EPPK1 as a Prognostic Biomarker in Type I Endometrial Cancer and Its Correlation with Immune Infiltration.

Purpose: Approximately 20% of patients with type I endometrial cancer (EC) of the uterus experience recurrence and metastasis. However, existing data do not provide sufficient evidence for the utility of protein levels as prognostic biomarkers in type I EC. This study aims to determine whether epiplakin1 (EPPK1) and progesterone receptor (PR) play a role in the recurrence and metastasis of type I EC. Methods: Following the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) for assessing the quality of biomarker research results, a retrospective analysis was conducted on clinical information and tissue samples of type I EC patients. Protein expression data and clinical data for type I EC were downloaded from The Cancer Proteome Atlas (TCPA) database. We utilized the Kaplan-Meier (K-M) method and Cox proportional hazards regression analyses to evaluate whether epiplakin1 (EPPK1), progesterone receptor (PR) and certain clinical parameters can serve as independent prognostic factors. The Immune Cell Abundance Identifier (ImmuCellAI) and Cancer Immunome Atlas (TCIA) were employed to predict responses to immunotherapy. Immunohistochemistry was carried out to assess the expression of EPPK1 in type I EC. Results: Type I EC patients with high EPPK1 and low PR expression had higher International Federation of Gynecology and Obstetrics (FIGO) stage, recurrence, and metastasis rates. Furthermore, EPPK1 was identified as an independent prognostic factor, and low expression of EPPK1 was predominantly observed in the POLE ultramutated (POLEmut) group, indicating a favorable prognosis. Additionally, the high EPPK1 expression group had a lower Immune Prognostic Score (IPS), suggesting that the high-expression group may not benefit from immune checkpoint inhibitors. Conclusion: High expression of EPPK1 is an independent prognostic factor in type I EC patients with low PR expression. It can identify a subgroup of patients at high risk of recurrence. A more aggressive treatment approach is recommended for these patients.

Structurally diverse oxygen-containing aromatic compounds with anti-inflammatory activity from Aspergillus sp. LY-1-2.

Three isocoumarins, ascoisocoumarin A (1), embeurekol (2), and sclerotinin A (3), and five biosynthetically related derivatives, ascospinols A-C (4, 6, and 7), and talaflavuols C and B (5 and 8), together with twelve polyketides or terpenes (9-20) were isolated from the fungus Aspergillus sp. LY-1-2 inhabited in a sample of Cordyceps sp. Most of them belong to the family of oxygen-containing aromatic compounds and compounds 1, 4, 6, and 7 are previously undescribed compounds. Their planar structures were established by a combined spectroscopic analysis of HRESIMS and NMR, and their stereochemistry was determined by 13C NMR calculations with sorted training set (STS) protocol analysis, and ECD calculations. New compounds 1 and 6 displayed potential anti-inflammatory effects in lipopolysaccharide (LPS)-induced BV2 microglia cells.

Comparison of Machine Learning Models Using Diffusion-Weighted Images for Pathological Grade of Intrahepatic Mass-Forming Cholangiocarcinoma.

Is the radiomic approach, utilizing diffusion-weighted imaging (DWI), capable of predicting the various pathological grades of intrahepatic mass-forming cholangiocarcinoma (IMCC)? Furthermore, which model demonstrates superior performance among the diverse algorithms currently available? The objective of our study is to develop DWI radiomic models based on different machine learning algorithms and identify the optimal prediction model. We undertook a retrospective analysis of the DWI data of 77 patients with IMCC confirmed by pathological testing. Fifty-seven patients initially included in the study were randomly assigned to either the training set or the validation set in a ratio of 7:3. We established four different classifier models, namely random forest (RF), support vector machines (SVM), logistic regression (LR), and gradient boosting decision tree (GBDT), by manually contouring the region of interest and extracting prominent radiomic features. An external validation of the model was performed with the DWI data of 20 patients with IMCC who were subsequently included in the study. The area under the receiver operating curve (AUC), accuracy (ACC), precision (PRE), sensitivity (REC), and F1 score were used to evaluate the diagnostic performance of the model. Following the process of feature selection, a total of nine features were retained, with skewness being the most crucial radiomic feature demonstrating the highest diagnostic performance, followed by Gray Level Co-occurrence Matrix lmc1 (glcm-lmc1) and kurtosis, whose diagnostic performances were slightly inferior to skewness. Skewness and kurtosis showed a negative correlation with the pathological grading of IMCC, while glcm-lmc1 exhibited a positive correlation with the IMCC pathological grade. Compared with the other three models, the SVM radiomic model had the best diagnostic performance with an AUC of 0.957, an accuracy of 88.2%, a sensitivity of 85.7%, a precision of 85.7%, and an F1 score of 85.7% in the training set, as well as an AUC of 0.829, an accuracy of 76.5%, a sensitivity of 71.4%, a precision of 71.4%, and an F1 score of 71.4% in the external validation set. The DWI-based radiomic model proved to be efficacious in predicting the pathological grade of IMCC. The model with the SVM classifier algorithm had the best prediction efficiency and robustness. Consequently, this SVM-based model can be further explored as an option for a non-invasive preoperative prediction method in clinical practice.

Broadband radar absorbing metamaterial based on Al @SiO2 conductive composite film.

Artificially designed metamaterial structures can manipulate electromagnetic waves, endowing them with exotic physical properties that are not found in natural materials, such as negative refractive index, superlens, and inverse Doppler effect. These characteristics are widely applied in various engineering and military applications. Due to increasingly complex application environments and innovation in radar detection technology, the combination of broadband absorption performance under thin thickness and efficient preparation methods at low cost is often the focus of research on new generation stealth materials. Here, we propose Al@SiO2 composite conductive film metamaterial (Al@SiO2 CCFM) to achieve wideband absorption of electromagnetic waves. This metamaterial structure combines two resonant units, resulting in three absorption bands in the absorption curve. The results show that the absorption rate of the metamaterial is above 90% in the frequency range of 10.6 GHz to 26.0 GHz. The resonance mechanism between multiple structures is a prerequisite for achieving wideband absorption. The materials Al and SiO2 used in Al@SiO2 CCFM are inexpensive and abundant, and the fabrication method is simple. Therefore, they hold great potential for large-scale applications in the multispectral stealth and electromagnetic shielding field.

Comparative study on the effects of different polishing methods on tooth surface microstructure and roughness following initial periodontal treatment.

OBJECTIVE: To investigate the effects of different polishing methods on the surface microstructure and roughness of teeth following initial periodontal treatment. METHODS: Teeth were divided into three groups (silica onegloss, polishing disc, and polishing strip) in vitro. Tooth surface microstructure was characterized via scanning electron microscopy. Roughness was measured by profilometry and laser scanning confocal microscopy (LSCM). According to the in vitro results, one group was chosen for further clinical trials. Effects of the chosen polishing method on patient plaque control and satisfaction were assessed via plaque staining and visual analog scale (VAS). RESULTS: Electron microscopy results revealed that the polishing disc group had smoother roots and crowns than did the other two groups. Roughness analysis revealed that the crown roughness with the polishing disc and silica onegloss was lower, and the root roughness with the polishing disc was the lowest (p < .05) The LSCM results showed that the pigment deposition depth with the polishing disc and silicon onegloss in the crowns and roots were significantly lower than those with the other two methods (p = .000). The polishing effect of the polishing disc was best among the three groups. Clinical trials were performed to verify the polishing disc effects. Plaque staining results showed that the decrease in plaque in the polishing disc group was greater than that of the rubber cup group (p = .020), which was similar to the results of LSCM. The VAS results showed that the polishing disc made teeth feel smoother, similar to the results of the roughness detection, and the procedure was more comfortable (p < .05). However, there was no significant difference between the two groups regarding foreign body sensation during pronunciation (p = .178). CONCLUSION: Combining in vitro and in vivo evaluations, the use of a polishing disc following periodontal treatment yielded superior polishing effects on teeth and was better accepted by patients.

UCHL-3 as a potential biomarker of ovarian cancer.

OBJECTIVE: This study explored promising prognostic and immune therapeutic candidate biomarkers for OC and determined the expression, prognostic value, and immune effects of UCHL3. METHODS: UCHL3 expression and clinical data were investigated using bioinformatic analysis. CCK8 and transwell assays were conducted to evaluate the impact of UCHL3 on proliferation and migration, and the effects of UCHL3 were further validated in a mouse model. Univariate and least absolute shrinkage and selection operator regression analyses were performed to construct a novel UCHL3-related prognostic risk model. Gene set enrichment analysis (GSEA) and immune analysis were performed to identify the significantly involved functions of UCHL3. Finally, bioinformatic analysis and immunohistochemistry were performed to explore the effect of UCHL3 on chemotherapy. RESULTS: UCHL3 expression was upregulated and associated with worse overall survival (OS) in OC. UCHL3 depletion repressed cell proliferation and migration both in vitro and in vivo. Furthermore, 237 genes were differentially expressed between the high and low UCHL3 expression groups. Subsequently, a UCHL3-related prognostic signature was built based on six prognostic genes (PI3, TFAP2B, MUC7, PSMA2, PIK3C2G, and NME1). Independent prognostic analysis suggested that age, tumor mutational burden, and RiskScore can be used as independent prognostic factors. The immune infiltration analysis and GSEA suggested that UCHL3 expression was related to the immune response. In addition, UCHL3 expression was higher in platinum-resistant OC patients than in platinum-sensitive patients. UCHL3 overexpression was associated with poorer OS. CONCLUSION: UCHL3 overexpression contributes to aggressive progression, poor survival, and chemoresistance in OC. Therefore, UCHL3 may be a candidate prognostic biomarker and potential target for controlling progression and platinum resistance in OC.

Identification and characterization of multipotential stem cells in immortalized normal ovarian surface epithelial cells.

The ovarian surface epithelium (OSE) is a single layer of squamous-to-cuboidal epithelial cells that experience repetitive ovulatory rupture and subsequent repair. However, the characteristics of human immortalized ovarian surface epithelial cells (IOSE80) remain elusive. This study aims to determine whether IOSE80 cells have the characteristics of stem cell proliferation and multilineage differentiation and their application in regenerative medicine. IOSE80 cells are sequenced by high-throughput transcriptome analysis, and 5 sets of public data are used to compare the differences between IOSE80 cells and bone marrow mesenchymal stem cells, pluripotent stem cells, and oocytes in transcriptome profiling. The IOSE80 cells present a cobblestone-like monolayer and express the epithelial cell marker KRT18; the stem cell markers IFITM3, ALDH1A1, and VIM; lowly express stem cell marker LGR5 and germ cell markers DDX4 and DAZL. In addition, the GO terms "regulation of stem cell proliferation", "epithelial cell proliferation", etc., are significantly enriched ( P<0.05). IOSE80 cells have the potential to act as mesenchymal stem cells to differentiate into adipocytes with lipid droplets, osteoblasts, and chondroblasts in vitro. IOSE80 cells express pluripotent stem cell markers, including OCT4, SSEA4, TRA-1-60, and TRA-1-81, and they can be induced into three germ layers in vitro. IOSE80 cells also form oocyte-like cells in vitro and in vivo. In addition, IOSE80 cells exhibit robust proliferation, migration, and ovarian repair functions after in vivo transplantation. This study demonstrates that IOSE80 cells have the characteristics of pluripotent/multipotent stem cells, indicating their important role in tissue engineering and regenerative medicine.

Analyzing gully erosion and deposition patterns in loess tableland: Insights from small baseline subset interferometric synthetic aperture radar (SBAS InSAR).

The fragile Loess Plateau of China suffers substantial gully erosion. It is imperative to elucidate gully erosion patterns for implementing effective erosion control strategies. However, high spatiotemporal resolution quantification of gully dynamics remains limited across the Loess Plateau landscape. We utilized the small baseline subset interferometric synthetic aperture radar (SBAS InSAR) technique to investigate the phenomenon of gully erosion and deposition on the Dongzhiyuan tableland, which sits within the vast expanse of the Loess Plateau in China, over the period spanning 2020-2022. The tableland edges subsided while gully bottoms uplifted due to sedimentation. Low elevations underwent active deformation. Slope, aspect, and curvature modulated uplift and subsidence patterns by affecting runoff and sediment transport. Gentle downstream slopes displayed enhanced sedimentation. Southern gullies showed pronounced uplift compared to northern gullies. Heavy rainfall triggered extensive erosion followed by rapid uplift, reflecting an adaptive oscillation between erosion and deposition. Basin hydrology correlated with spatial patterns of deformation. Vegetation cover above 60 % of the maximum substantially increased InSAR error. Our study reveals intricate spatiotemporal behaviors of erosion and deposition in loess gullies using time-series InSAR. The findings provide new insights into gully geomorphology and evolution, and our study quantifies gully erosion and deposition patterns at high spatiotemporal resolution, enabling identification of the most vulnerable areas and prioritization of conservation efforts.

Utility of Goal Attainment Scaling (GAS) in evaluating a multicomponent exercise programme for community-dwelling pre-frail older adults.

OBJECTIVES: This study aimed to investigate the effectiveness of Goal Attainment Scaling (GAS) in assessing an intervention for pre-frail senior citizens. Additionally, the study aimed to explain how the GAS goals were established based on the International Classification of Functioning, Disability and Health (ICF) categories, including body function, activity and participation and environmental factors. METHODS: In this study, 220 pre-frail older adults were randomly selected to participate in a controlled trial. The intervention group engaged in multicomponent exercise three times a week, once at a community health service location and twice at home. The control group received advice on physical activity but did not have supervised exercise. Participants in both groups selected individualised GAS goals from 23 goals developed based on ICF by focus group discussion. The study used generalised estimating equations to analyse the differences between the groups. RESULTS: The study included 144 participants, 72 in the exercise group and 72 in the control group. The top three individualised goals for all participants were vestibular functions (53.5%), pain management (43.1%) and lifting and carrying objects (31.9%). Both groups saw a significant increase in GAS scores at week 8 and week 24 of the intervention (p<0.05), but the exercise group showed a more significant improvement (p<0.05). The participants living alone were associated with lower postintervention improvements in the GAS scores. In contrast, the participants who were using a smartphone were likely to get higher postintervention improvements in the GAS scores. CONCLUSIONS: GAS can be a valuable tool for setting and evaluating individualised and meaningful goals in body functions, activity and participation and environmental factors. The multicomponent exercise interventions can help pre-frail older adults achieve their expected goals as measured by the GAS.

Functional Composite Dual-Phase In Situ Self-Reconstruction Design for High-Energy-Density Li-Rich Cathodes.

The unique anionic redox mechanism provides, high-capacity, irreversible oxygen release and voltage/capacity degradation to Li-rich cathode materials (LRO, Li1.2 Mn0.54 Co0.13 Ni0.13 O2 ). In this study, an integrated stabilized carbon-rock salt/spinel composite heterostructured layers (C@spinel/MO) is constructed by in situ self-reconstruction, and the generation mechanism of the in situ reconstructed surface is elucidated. The formation of atomic-level connections between the surface-protected phase and bulk-layered phase contributes to electrochemical performance. The best-performing sample shows a high increase (63%) of capacity retention compared to that of the pristine sample after 100 cycles at 1C, with an 86.7% reduction in surface oxygen release shown by differential electrochemical mass spectrometry. Soft X-ray results show that Co3+ and Mn4+ are mainly reduce in the carbothermal reduction reaction and participate in the formation of the spinel/MO rock-salt phase. The results of oxygen release characterized by Differential electrochemical mass spectrometry (DEMS) strongly prove the effectiveness of surface reconstruction.

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5.

Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycin-producing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure-activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a ß-catenin signaling pathway.

Molecular modification and biotechnological applications of microbial aspartic proteases.

The growing preference for incorporating microbial aspartic proteases in industries is due to their high catalytic function and high degree of substrate selectivity. These properties, however, are attributable to molecular alterations in their structure and a variety of other characteristics. Molecular tools, functional genomics, and genome editing technologies coupled with other biotechnological approaches have aided in improving the potential of industrially important microbial proteases by addressing some of their major limitations, such as: low catalytic efficiency, low conversion rates, low thermostability, and less enzyme yield. However, the native folding within their full domain is dependent on a surrounding structure which challenges their functionality in substrate conversion, mainly due to their mutual interactions in the context of complex systems. Hence, manipulating their structure and controlling their expression systems could potentially produce enzymes with high selectivity and catalytic functions. The proteins produced by microbial aspartic proteases are industrially capable and far-reaching in regulating certain harmful distinctive industrial processes and the benefits of being eco-friendly. This review provides: an update on current trends and gaps in microbial protease biotechnology, exploring the relevant recombinant strategies and molecular technologies widely used in expression platforms for engineering microbial aspartic proteases, as well as their potential industrial and biotechnological applications.

Heterodimers of Aromadendrane Sesquiterpenoid with Benzoquinone from the Chinese Liverwort Mylia nuda.

Mylnudones A-G (1-7), unprecedented 1,10-seco-aromadendrane-benzoquinone-type heterodimers, and a highly rearranged aromadendrane-type sesquiterpenoid (8), along with four known analogs (9-12), were isolated from the liverwort Mylia nuda. Compounds 1-6 and 7, bearing tricyclo[6.2.1.02,7] undecane and tricyclo[5.3.1.02,6] undecane backbones, likely formed via a Diels-Alder reaction and radical cyclization, respectively. Their structures were determined by spectroscopic analysis, computational calculation, and single-crystal X-ray diffraction analysis. Dimeric compounds displayed cytoprotective effects against glutamic acid-induced neurological deficits.

Concurrent glomerular PCDH7 deposits in PLA2R-associated membranous nephropathy.

The understanding of membranous nephropathy (MN) has undergone impressive advancements in the last 5 years, particularly due to identification of novel antigenic targets. M-type phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) account for approximately 70% and 1-5% of the target antigens in primary MN, respectively. Recently, more novel/putative antigens have been identified in the remaining cases of MN that include exostosin 1/exostosin 2 (EXT1/EXT2), neural epidermal growth factor-like 1 protein (NELL-1), semaphorin 3B (SEMA3B) and protocadherin 7 (PCDH7). However, comparatively little is known about the PCDH7 among these novel antigens. As such, we herein described a unique case of positive glomerular PCDH7 deposits in PLA2R-associated MN, which may offer a deeper insight into the role of PCDH7 in MN and improve our understanding of glomerular diseases in the post-COVID era, particularly with the emerging variants.

Wettability of Ionic Liquids in High Magnetic Fields.

Here, we demonstrate that high magnetic fields alter the wettability of water and ionic solutions on the single-crystal α-Al2O3. We investigated the relationship between the substrate crystal orientation, material magnetism, liquid conductivity, and the surface contact angle. Applying high magnetic fields decreased the water contact angles on all of the surface orientations studied, and the reduction was larger for more magnetic substrates. For ionic solutions, high magnetic fields increased the contact angle on the (0001) α-Al2O3 surface but decreased the contact angles on the (112̅0), (101̅0), and (011̅2) surfaces. We attribute these orientation-dependent ionic solution responses to competition between the field-induced sample magnetization energy and the Lorentz force acting on the ionic solution. Overall, this work provides new magnetic-field-based strategies for changing the wettability and provides guidelines for fabricating novel microfluidic systems or biointerfaces with in situ magnetic control.

[Evaluation of red and white aesthetic effects of porcelain veneers in the restoration of developmental anterior dental gaps].

PURPOSE: To evaluate the red and white aesthetic effect of porcelain veneer in the restoration of developmental anterior interdental spaces. METHODS: A total of 152 anterior teeth in 64 patients with developmental anterior dental gaps were restored using porcelain veneers, the aesthetic effects before and after restoration were evaluated by pink aesthetic index (PES) and white aesthetic index(WES), the aesthetic effect of gingival papilla filling and reconstruction was evaluated by interdental gingival papilla index (PIS), and visual analogue score (VAS) was used to compare the satisfaction of patients before and after restoration. SPSS 203.0 software package was used for statistical analysis. RESULTS: The overall mean scores of PES before and after restoration of 152 developmental anterior interdental teeth were 9.63±2.23 and 13.64±0.88, respectively. The average scores of WES before and after restoration were 6.85±1.87 and 9.81±0.58, respectively. There were significant differences of PES and WES scores before and after restoration(P＜0.01). According to the requirements of "near" perfect restoration(PES≥13 points, WES≥9 points), the red and white aesthetic effect after restoration was near the standard. The scores of PIS before and after restoration were 1.86±0.67 and 2.97±0.18, the interdental gingival papilla was completely filled with space, and the shape was ideal, there were significant statistical differences before and after restoration(P＜0.01). Patients were more satisfied with the smile curve and morphology of the restored anterior teeth than other parameters. CONCLUSIONS: The aesthetic effect of using porcelain veneers to repair developmental anterior interdental gaps is ideal, among which the filling of the papillae between the teeth can meet the expectations of patients, and the aesthetic effect evaluation of PIS and PES/WES applied to porcelain veneers to repair developmental anterior interdental spaces has practical guiding significance in clinical practice.

Improved Electrochemical Performance of Li-Rich Cathode Materials via Spinel Li2MoO4 Coating.

Li-rich manganese-based cathode materials (LRMs) are considered one of the most promising cathode materials for the next generation of lithium-ion batteries (LIBs) because of their high energy density. However, there are problems such as a capacity decay, poor rate performance, and continuous voltage drop, which seriously limit their large-scale commercial applications. In this work, Li1.2Mn0.54Co0.13Ni0.13O2 coated with Li2MoO4 with a unique spinel structure was prepared with the wet chemistry method and the subsequent calcination process. The Li2MoO4 coating layer with a spinel structure could provide a 3D Li+ transport channel, which is beneficial for improving rate performance, while protecting LRMs from electrolyte corrosion, suppressing interface side reactions, and improving cycling stability. The capacity retention rate of LRMs coated with 3 wt% Li2MoO4 increased from 69.25% to 81.85% after 100 cycles at 1 C, and the voltage attenuation decreased from 7.06 to 4.98 mV per cycle. The lower Rct also exhibited an improved rate performance. The results indicate that the Li2MoO4 coating effectively improves the cyclic stability and electrochemical performance of LRMs.

Ent-eudesmane sesquiterpenoids from the Chinese liverwort Chiloscyphus polyanthus.

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.

The GLCCI1 rs37973 variant and the efficacy of inhaled corticosteroids in the treatment of asthma: A meta-analysis.

OBJECTIVE: This study investigated the relationship between the glucocorticoid-induced transcript 1 (GLCCI1) gene variant and the degree of improvement in lung function with inhaled corticosteroids (ICS). METHODS: We searched the PubMed, Embase, Cochrane Library, CBM, CNKI and Wanfang databases to obtain studies on the GLCCI1 rs37973 variant and the efficacy of ICS in asthma. RESULTS: The overall meta-analysis showed that patients with the GG phenotype (mutant homozygotes) exhibited significantly smaller forced expiratory volume in 1 sec (FEV1) change than patients with the AG phenotype (mutant heterozygous) (MD = -0.08, 95% CI [-0.12, -0.03], P = 0.001). Compared with the AA phenotype (wild homozygotes), the GG phenotype (MD = -4.23, 95% CI [-6.09, -2.38], P < 0.00001) and AG phenotype (MD = -1.92, 95% CI [-2.35, -1.49], P < 0.00001) had significantly smaller FEV1%pred changes. The FEV1 change subgroup analysis showed that the GG phenotype group was smaller than the AA phenotype group at 8 (MD = -0.53, 95% CI [-0.91, -0.14], P = 0.007), 12 (MD = -0.16, 95% CI [-0.30, -0.02], P = 0.02) and 24 (MD = -0.09, 95% CI [-0.17, -0.01], P = 0.02) weeks of treatment; the GG phenotype group was smaller than the AG phenotype group at 12 weeks (MD = -0.08, 95% CI [-0.15, -0.01], P = 0.02). CONCLUSION: This meta-analysis suggests that the GLCCI1 rs37973 variant affects the efficacy of ICS and that the presence of the G allele attenuates the improvement in lung function with ICS.

Interconvertible Pyridone Alkaloids from the Marine-Derived Fungus Penicillium oxalicum QDU1.

Eleven new pyridone alkaloids, penicipyridones A-K (1-11), and three new tetramic acids, tolypocladenols D-F (12-14), were isolated from rice media cultures of the marine-derived fungus Penicillium oxalicum QDU1. Their structures, including absolute configurations, were determined by comprehensive analyses of spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction data. Interestingly, several of the penicipyridones undergo interconversions between hydroxy and methoxy groups at C-4 in acidic MeOH solution. Furthermore, in an acidic aqueous solution, OH-4 could be replaced by diverse substituent groups. Compounds 1, 4, 5, 8, 10, 11, and 14 exhibited moderate inhibitory effects on NO production in the LPS-induced RAW264.7 macrophages, with IC50 values ranging from 9.2 to 19 µM.