Osteoprotective effect of Achyranthes bidentata root extract on osteoporotic rats: a systematic review and meta-analysis.

CONTEXT: Achyranthes bidentata Blume (ABB), a plant of Amaranthaceae family, has been one of the more commonly used phytomedicine remedies for thousands of years, and recent studies have highlighted the efficacy of its extracts in the treatment of osteoporosis. Nonetheless, a thorough analysis of its benefits is currently absent. OBJECTIVE: This meta-analysis assessed the effects of ABB root extract (ABBRE) on osteoporotic rats and provides a rationale for future clinical studies. METHODS: Searches were conducted in seven different Chinese and English databases, and the search period was from their establishment to January 2024. This study was registered in PROSPERO (CRD42023418917). Selected research regarding the ABBRE treatment of osteoporotic rats, and the corresponding research has distinctly reported outcomes, and the data on the bone mineral density (BMD), bone histomorphometrics, biomechanical parameters, and bone biochemical markers of osteoporotic rats can be extracted. RESULTS: Through screening, 11 studies met the eligibility requirements for inclusion, in which 222 animals were studied. The treatment group with ABBRE exhibited increased bone mineral density (standardized mean difference [SMD] = 1.64, 95% CI = 0.52 to 2.77). Based on subgroup analysis, the greatest increase in bone mineral density was observed when the dose of ABBRE was ≤ 400 mg/kg/day and the duration of treatment was ≤ 12 weeks. CONCLUSIONS: ABBRE is a phytomedicine that can effectively promote the enhancement of bone mineral density and ease osteoporosis. It can be developed into a new alternative therapy by conducting experiments and clinical studies on larger samples.

Wearable Applicability of Respiratory Airflow Transducers: Current Approaches and Future Directions.

Advanced technologies employed in modern respiratory airflow transducers have exhibited powerful capabilities in accurately measuring respiratory flow under controlled and sedentary conditions, particularly in clinical settings. However, the wearable applicability of these transducers as face-mounted electronics for use in occupational and sporting activities remains unexplored. The present review addresses the critical wearability issue associated with current respiratory airflow transducers, including pneumotachographs, orifice flowmeters, turbine flowmeters, hot wire anemometers, ultrasound flowmeters, and piezoelectric airflow transducers. Furthermore, a comprehensive analysis and comparison of all factors that impact the wearable applicability of respiratory airflow transducers are conducted, considering dynamic accuracy, long-term usability, power consumption, calibration frequency, and cleaning requirements. The findings indicate that the piezoelectric airflow transducer stands out as a more viable option for wearables compared to other devices. We expect that this review will serve as a valuable engineering reference, guiding future research efforts in designing and developing wearable respiratory airflow transducers for ambulatory respiratory flow monitoring.

Combinatory effect of ALA-PDT and itraconazole in the treatment of cutaneous protothecosis.

BACKGROUND: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. METHODS: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. RESULTS: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. CONCLUSIONS: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

Multifunctional pressure and humidity sensor modulated by electrostatic interactions and hydrogen bonds for wearable health monitoring.

Breathing and urination, are vital physiological activities of the human body, continuous real-time monitoring of these physiological behaviors could offer timely feedback on an individual's health status. However, current monitoring techniques predominantly rely on cumbersome and intricate medical apparatuses, posing challenges in adapting to the diverse requirements of multi-scenario detection. Consequently, there is a growing interest in developing wearable devices capable of monitoring breathing and urination. In this work, we developed a multifunctional sensor integrating humidity and pressure sensing modes using a simple dip-coating process. By introducing sodium carboxymethyl cellulose and conductive polyaniline hybrid intercalation between MXene layers, a stable conductive network is established through hydrogen bonds and electrostatic interactions among materials. The overall electromechanical properties of the composites will be well improved. And, the effects of different conductive filler ratios and the number of dipping times on the construction of conductive networks are investigated. The multifunctional sensor exhibited improved sensing characteristics, including detecting pressures up to 532 kPa and a sensitivity of 19.58 kPa-1. Furthermore, it also demonstrates good humidity-sensing capabilities. Tests on volunteers demonstrated the potential in the detection of breathing and urination. In addition, the sensors are capable of transmitting Morse code. This interesting application will offer the possibility of normal communication for people with speech impairments. Given its utility and sustainability, the sensor has potential for applications in wearable health monitoring, intelligent life and telemedicine.

Jasmonic acid plays an important role in mediating retrograde signaling under mitochondrial translational stress to balance plant growth and defense.

Proper mitochondrial function is crucial to plant growth and development. Inhibition of mitochondrial translation leads to mitochondrial proteotoxic stress, which triggers a protective transcriptional response that regulates nuclear gene expression, commonly referred to as the mitochondrial unfolded protein response (UPRmt). Although UPRmt has been extensively studied in yeast and mammals, very little is known about UPRmt in plants. Here, we show that mitochondrial translational stress inhibits plant growth and development by inducing jasmonic acid (JA) biosynthesis and signaling. The inhibitory effect of mitochondrial translational stress on plant growth was alleviated in JA signaling defective mutants coi1-2, myc2, and myc234. Genetic analysis indicates that Arabidopsis mitochondrial ribosomal protein L1 (MRPL1), a key factor in UPRmt, regulates plant growth in a CORONATINE-INSENSITIVE1 (COI1)-dependent manner. Moreover, under mitochondrial translational stress, MYC2 showed direct binding to G-boxes in the ETHYLENE RESPONSE FACTOR 109 (ERF109) promoter. The induction of ERF109 expression enhances hydrogen peroxide (H2O2) production, which acts as a feedback loop to inhibit root growth. In addition, mutation of MRPL1 increases JA accumulation, reduces plant growth, and enhances biotic stress resistance. Overall, our findings reveal that JA plays an important role in mediating retrograde signaling under mitochondrial translational stress to balance plant growth and defense.

Magnetic Field Assisted Enhanced Sensitivity of Nonferromagnetic Materials Boosting the Carrier Transfer: Mechanistic Studies.

The performance of semiconductor sensors is determined by reaction kinetics, conductivity, and electron mobility, which are undoubtedly closely related to the electron motion behavior. Therefore, the effective regulation of electronic states is crucial for improving gas sensing properties. Previous methods of enhancing the gas-sensing performance have induced complex material modifications, and the extent of performance improvement is usually very limited. Further optimization of the gas sensing performance requires continuous efforts to advance new technologies. Toward this issue, a novel magnetic field-induced strategy is adopted to boost the carrier transfer efficiency of nonferromagnetic semiconductors. The gas sensing investigation results manifest that the applied magnetic field can effectively enhance the sensitivity and reduce the baseline resistance. The In2O3 NC-2 (In2O3 nanocubes) with an applied magnetic field have a greatly enhanced response of 161.4 toward 100 ppm formaldehyde, which is 2.5 times higher than that without magnetic field. The enhanced gas sensing properties can be mainly attributed to magnetization of reactive materials, which makes the orientation of electronic magnetic moments consistent, thus greatly contributing to reactivity. This work introduces a practical approach to effectively improve gas sensing performance without further morphology optimization, noble metal catalysis, structural modification, and material cladding. The results of this study provide new insights for designing novel gas sensors to improve the gas sensing performance.

Artificial intelligence-enabled multipurpose smart detection in active-matrix electrowetting-on-dielectric digital microfluidics.

An active-matrix electrowetting-on-dielectric (AM-EWOD) system integrates hundreds of thousands of active electrodes for sample droplet manipulation, which can enable simultaneous, automatic, and parallel on-chip biochemical reactions. A smart detection system is essential for ensuring a fully automatic workflow and online programming for the subsequent experimental steps. In this work, we demonstrated an artificial intelligence (AI)-enabled multipurpose smart detection method in an AM-EWOD system for different tasks. We employed the U-Net model to quantitatively evaluate the uniformity of the applied droplet-splitting methods. We used the YOLOv8 model to monitor the droplet-splitting process online. A 97.76% splitting success rate was observed with 18 different AM-EWOD chips. A 99.982% model precision rate and a 99.980% model recall rate were manually verified. We employed an improved YOLOv8 model to detect single-cell samples in nanolitre droplets. Compared with manual verification, the model achieved 99.260% and 99.193% precision and recall rates, respectively. In addition, single-cell droplet sorting and routing experiments were demonstrated. With an AI-based smart detection system, AM-EWOD has shown great potential for use as a ubiquitous platform for implementing true lab-on-a-chip applications.

Association of triglyceride-glucose index with severity of coronary artery disease among male patients.

The correlation between diabetes and coronary artery disease (CAD) is well established. Insulin resistance (IR) is considered a primary contributor to elevated CAD risk in diabetic individuals. The triglyceride-glucose (TyG) index serves as a straightforward surrogate marker for insulin resistance. However, few studies have explored their correlations with myocardial infarction and CAD severity. Therefore, our study aimed to investigate the association between the TyG index and the occurrence of myocardial infarction, as well as the severity of coronary artery disease. We conducted a retrospective study involving 3865 consecutive patients who underwent coronary angiography at the First Affiliated Hospital of Zhejiang University, School of Medicine. Of these, 1724 patients were diagnosed with coronary artery disease. Demographic, biochemical, clinical, and angiographic data were gathered. A robust correlation exists between the TyG index and CAD subtypes, suggesting its potential as an independent clinical diagnostic marker. Moreover, the TyG index exhibited a significant positive correlation with disease severity, as assessed by the Gensini score. Elevated TyG index was associated with an increased predisposition to severe CAD, as indicated by the Gensini score, and myocardial infarction, even after adjusting for well-established cardiovascular risk factors.

Insight into the compositional variation of volatile and polar compounds of Radix Bupleuri from different processing technologies by GC-MS and UHPLC-Q-TOF/MS metabolomics.

INTRODUCTION: Insight into comparing key active ingredients of Radix Bupleuri (RB) based on different processing technologies is a key step to reveal the material basis of drug efficacy and a challenging task for developing traditional Chinese medicine (TCM). OBJECTIVE: This work aims to establish a comprehensive comparative analysis method of TCM and its processed products, which can be used to analyze the changing trend of active components of RB before and after processing. METHODS: First, RB was processed with rice vinegar, rice wine, and honey. Then, ultra-high-performance liquid chromatography (UHPLC) and gas chromatography (GC) coupled with mass spectrometry (MS) technology as well as multiple statistical analyses were used to comprehensively evaluate the compositional variation of polar and volatile compounds in RB under different processing processes. Meanwhile, in UHPLC-MS, a sequential window acquisition of all theoretical fragment ion spectral and information-dependent acquisition mutual authentication (SIMA) was developed. RESULTS: A total of 30 polar components and 33 volatile components were identified as chemical markers (mainly type II saikosaponins, terpenes, and fatty acid esters). These may be the material basis for giving unique pharmacological activities to RB and its processed products. CONCLUSIONS: These findings provided a solid foundation for the differentiated clinical application of RB, and the SIMA method held great potential for achieving accurate analysis of TCM processing ingredients.

The First Case of Intra-portal Islet Implantation During Liver Machine Perfusion Allowing Simultaneous Islet-liver Transplantation in A Human: A New and Safe Treatment for End-stage Liver Disease Combined With Diabetes Mellitus.

OBJECTIVE: Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). BACKGROUND: DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. METHODS: We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. RESULTS: The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. CONCLUSIONS: This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

Deep Learning in Gene Regulatory Network Inference: A Survey.

Understanding the intricate regulatory relationships among genes is crucial for comprehending the development, differentiation, and cellular response in living systems. Consequently, inferring gene regulatory networks (GRNs) based on observed data has gained significant attention as a fundamental goal in biological applications. The proliferation and diversification of available data present both opportunities and challenges in accurately inferring GRNs. Deep learning, a highly successful technique in various domains, holds promise in aiding GRN inference. Several GRN inference methods employing deep learning models have been proposed; however, the selection of an appropriate method remains a challenge for life scientists. In this survey, we provide a comprehensive analysis of 12 GRN inference methods that leverage deep learning models. We trace the evolution of these major methods and categorize them based on the types of applicable data. We delve into the core concepts and specific steps of each method, offering a detailed evaluation of their effectiveness and scalability across different scenarios. These insights enable us to make informed recommendations. Moreover, we explore the challenges faced by GRN inference methods utilizing deep learning and discuss future directions, providing valuable suggestions for the advancement of data scientists in this field.

Comparative transcriptomic and metabolomic analyses provide insights into the responses to high temperature stress in Alfalfa (Medicago sativa L.).

High temperature stress is one of the most severe forms of abiotic stress in alfalfa. With the intensification of climate change, the frequency of high temperature stress will further increase in the future, which will bring challenges to the growth and development of alfalfa. Therefore, untargeted metabolomic and RNA-Seq profiling were implemented to unravel the possible alteration in alfalfa seedlings subjected to different temperature stress (25 ℃, 30 ℃, 35 ℃, 40 ℃) in this study. Results revealed that High temperature stress significantly altered some pivotal transcripts and metabolites. The number of differentially expressed genes (DEGs) markedly up and down-regulated was 1876 and 1524 in T30_vs_CK, 2, 815 and 2667 in T35_vs_CK, and 2115 and 2, 226 in T40_vs_CK, respectively. The number for significantly up-regulated and down-regulated differential metabolites was 173 and 73 in T30_vs_CK, 188 and 57 in T35_vs_CK, and 220 and 66 in T40_vs_CK, respectively. It is worth noting that metabolomics and transcriptomics co-analysis characterized enriched in plant hormone signal transduction (ko04705), glyoxylate and dicarboxylate metabolism (ko00630), from which some differentially expressed genes and differential metabolites participated. In particular, the content of hormone changed significantly under T40 stress, suggesting that maintaining normal hormone synthesis and metabolism may be an important way to improve the HTS tolerance of alfalfa. The qRT-PCR further showed that the expression pattern was similar to the expression abundance in the transcriptome. This study provides a practical and in-depth perspective from transcriptomics and metabolomics in investigating the effects conferred by temperature on plant growth and development, which provided the theoretical basis for breeding heat-resistant alfalfa.

Artificial Intelligence Measurement of Preoperative Radiographs in Adolescent Idiopathic Scoliosis Based on Multiple-View Semantic Segmentation.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Imaging classification of adolescent idiopathic scoliosis (AIS) is directly related to the surgical strategy, but the artificial classification is complex and depends on doctors' experience. This study investigated deep learning-based automated classification methods (DL group) for AIS and validated the consistency of machine classification and manual classification (M group). METHODS: A total of 506 cases (81 males and 425 females) and 1812 AIS full spine images in the anteroposterior (AP), lateral (LAT), left bending (LB) and right bending (RB) positions were retrospectively used for training. The mean age was 13.6 ± 1.8. The mean maximum Cobb angle was 46.8 ± 12.0. U-Net semantic segmentation neural network technology and deep learning methods were used to automatically segment and establish the alignment relationship between multiple views of the spine, and to extract spinal features such as the Cobb angle. The type of each test case was automatically calculated according to Lenke's rule. An additional 107 cases of adolescent idiopathic scoliosis imaging were prospectively used for testing. The consistency of the DL group and M group was compared. RESULTS: Automatic vertebral body segmentation and recognition, multi-view alignment of the spine and automatic Cobb angle measurement were implemented. Compare to the M group, the consistency of the DL group was significantly higher in 3 aspects: type of lateral convexity (0.989 vs 0.566), lumbar curvature modifier (0.932 vs 0.738), and sagittal plane modifier (0.987 vs 0.522). CONCLUSIONS: Deep learning enables automated Cobb angle measurement and automated Lenke classification of idiopathic scoliosis whole spine radiographs with higher consistency than manual measurement classification.

Practical Performance Analysis of MDI-QKD with Orbital Angular Momentum on UAV Relay Platform.

The integration of terrestrial- and satellite-based quantum key distribution (QKD) experiments has markedly advanced global-scale quantum networks, showcasing the growing maturity of quantum technologies. Notably, the use of unmanned aerial vehicles (UAVs) as relay nodes has emerged as a promising method to overcome the inherent limitations of fiber-based and low-Earth orbit (LEO) satellite connections. This paper introduces a protocol for measurement-device-independent QKD (MDI-QKD) using photon orbital angular momentum (OAM) encoding, with UAVs as relay platforms. Leveraging UAV mobility, the protocol establishes a secure and efficient link, mitigating threats from untrusted UAVs. Photon OAM encoding addresses reference frame alignment issues exacerbated by UAV jitter. A comprehensive analysis of atmospheric turbulence, state-dependent diffraction (SDD), weather visibility, and pointing errors on free-space OAM-state transmission systems was conducted. This analysis elucidates the relationship between the key generation rate and propagation distance for the proposed protocol. Results indicate that considering SDD significantly decreases the key rate, halving previous data results. Furthermore, the study identifies a maximum channel loss capacity of 26 dB for the UAV relay platform. This result is pivotal in setting realistic parameters for the deployment of UAV-based quantum communications and lays the foundation for practical implementation strategies in the field.

PiRNA CFAPIR inhibits cardiac fibrosis by regulating the muscleblind-like protein MBNL2.

Myocardial fibroblasts transform into myofibroblasts during the progression of cardiac fibrosis, together with excessive cardiac fibroblast proliferation. Hence, the prevention and treatment of cardiac fibrosis are significant factors for inhibiting the development of heart failure. P-element Induced WImpy testis-interacting RNAs (PiRNA) are widely expressed in the heart, but their involvement in cardiac fibrosis has not yet been confirmed. We identified differentially expressed PiRNAs using Arraystar PiRNA expression profiling in Angiotensin II models of cardiac fibrosis in vivo and in vitro. We then explored cardiac-fibrosis-associated PiRNA-related proteins, RNA-protein interactomes, immunoprecipitation, and pulldown. We detected fibrosis markers and pathway-related proteins using immunofluorescence, qRT-PCR, and Western blot. We uncovered cardiac fibrosis associated PiRNA (CFAPIR) that was obviously dysregulated during cardiac fibrosis, whereas its overexpression reversed fibrosis in vivo and in vitro. Mechanistically, CFAPIR competitively bound muscleblind like protein 2 (MBNL2) and the cyclin-dependent kinase inhibitor P21 to regulate the TGF-ß1/SMAD3 signaling pathway.

Elevation of p53 sensitizes obese kidney to adriamycin-induced aberrant lipid homeostasis via repressing HNF4α-mediated FGF21 sensitivity.

INTRODUCTION: Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders appear progressively more severe after ADR-based chemotherapy in the obese state, and the specific molecular mechanism needs to be further clarified. OBJECTIVES: This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high-fat diet (HFD). METHODS: We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce an in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on the regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology, and in vitro approaches. RESULTS: Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF receptor-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor 4 alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. CONCLUSION: Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy.

MBNL2 promotes aging-related cardiac fibrosis via inhibited SUMOylation of Krüppel-like factor4.

Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-ß1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-ß1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

Atomic Layer Deposition of CeO2 Film with a Novel Heteroleptic Ce(III) Complex.

In this paper, four heteroleptic Ce(III) complexes, including Ce(thd)3-phen (thd = 2,2,6,6-tetramethyl-3,5-heptanedione, phen = 1, 10-phenanthroline (1), Ce(thd)3-MEDA (MEDA = N-Methylethylenediamine (2), Ce(thd)3-MOMA (MOMA = N-(2-Methoxyethyl)methylamine (3), and Ce(thd)3-DMDE (DMDE = N,N″-dimethyl ethanol amine (4), were synthesized and characterized with 1H-NMR, elemental analysis, and X-ray single-crystal diffraction. The thermogravimetric analysis and vapor pressure results indicated that the complexing ability of a nitrogen-containing bidentate ligand with a cerium ion was stronger than that of a mixed oxygen-nitrogen-containing bidentate ligand. Complex 2 was selected as an ALD precursor to deposit a CeO2 film on a SiO2/Si (100) wafer. The self-limited deposition results demonstrated that complex 2 was a potential ALD precursor.

Multi-omics Mendelian randomization integrating GWAS, eQTL and pQTL data revealed GSTM4 as a potential drug target for migraine.

INTRODUCTION: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. METHOD: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. RESULT: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. CONCLUSION: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.

DHA dietary intervention caused different hippocampal lipid and protein profile in ApoE-/- and C57BL/6J mice.

BACKGROUND: Changes in protein and lipid levels may occur in the Alzheimer's disease brain, and DHA can have beneficial effects on it. To investigate the impact of DHA dietary intervention on brain protein and lipid profile in ApoE-/- mice and C57 mice. METHOD: Three-month-old ApoE-/- mice and C57 mice were randomly divided into two groups respectively, and fed with control diet and DHA-fortified diet for five months. Cortical TC, HDL-C and LDL-C levels and cholesterol metabolism-related protein expression were measured by ELISA or immunohistochemistry methods. Hippocampus were collected for proteomic and lipidomics analysis by LC-MS/MS and differential proteins and lipid metabolites were screened and further analyzed by GO functional annotation and KEGG pathway enrichment analysis. RESULTS: DHA intervention decreased cortical TC level in both C57 and ApoE-/- mice (P < 0.05), but caused different change of cortical HDL-C, LDL-C level and LDL-C/HDL-C ratio in C57 and ApoE-/- mice (P < 0.05). Discrepant cortical and hippocampal LDLR, ABCG1, Lox1 and SORT1 protein expression was found between C57 and ApoE-/- mice (P < 0.05), and DHA treatment caused different changes of these proteins in C57 and ApoE-/- mice (P < 0.05). Differential hippocampal proteins and lipids profile were found in C57 and ApoE-/- mice before and after DHA treatment, which were mainly involved in vesicular transport and phospholipid metabolic pathways. CONCLUSION: ApoE genetic defect caused abnormal cholesterol metabolism, and affected protein and lipid profile, as well as discrepant response of hippocampal protein and lipids profile in the brain of mice given DHA fortified diet intervention.