Qian Yang Yu Yin Granule prevents hypertensive cardiac remodeling by inhibiting NLRP3 inflammasome activation via Nrf2.

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese poly-herbal formulation, has been validated in clinical trials to mitigate cardiac remodeling (CR), and cardiac damage in patients with hypertension. However, the specific mechanism remains unclear. AIM OF THE STUDY: This study explored the potential effects and potential mechanisms of QYYYG on hypertensive CR by combining various experimental approaches. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHRs) were used as a model of hypertensive CR, followed by QYYYG interventions. Blood pressure, cardiac function and structure, histopathological changes, and myocardial inflammation and oxidative stress were tested to assess the efficacy of QYYYG in SHRs. For in vitro experiments, a cell model of myocardial hypertrophy and injury was constructed with isoprenaline. Cardiomyocyte hypertrophy, oxidative stress, and death were examined after treatment with different concentrations of QYYYG, and transcriptomics analyses were performed to explore the underlying mechanism. Nrf2 and the ROS/NF-κB/NLRP3 inflammasome pathway were detected. Thereafter, ML385 and siRNAs were used to inhibit Nrf2 in cardiomyocytes, so as to verify whether QYYYG negatively regulates the NLRP3 inflammasome by targeting Nrf2, thereby ameliorating the associated phenotypes. Finally, high performance liquid chromatography (HPLC) was conducted to analyze the active ingredients in QYYYG, and molecular docking was utilized to preliminarily screen the compounds with modulatory effects on Nrf2 activities. RESULTS: QYYYG improved blood pressure, cardiac function, and structural remodeling and attenuated myocardial inflammation, oxidative stress, and cell death in SHRs. The transcriptomics results showed that the inflammatory response might be crucial in pathological CR and that Nrf2, which potentially negatively regulates the process, was upregulated by QYYYG treatment. Furthermore, QYYYG indeed facilitated Nrf2 activation and negatively regulated the ROS/NF-κB/NLRP3 inflammasome pathway, therefore ameliorating the associated phenotypes. In vitro inhibition or knockdown of Nrf2 weakened or even reversed the repressive effect of QYYYG on ISO-induced inflammation, oxidative stress, pyroptosis, and the NLRP3 inflammasome activation. Based on the results of HPLC and molecular docking, 30 compounds, including cafestol, genistein, hesperetin, and formononetin, have binding sites to Keap1-Nrf2 protein and might affect the activity or stability of Nrf2. CONCLUSION: In conclusion, the alleviatory effect of QYYYG on hypertensive CR is related to its regulation of Nrf2 activation. Specifically, QYYYG blocks the activation of the NLRP3 inflammasome by boosting Nrf2 signaling and depressing myocardial inflammation, oxidative stress, and pyroptosis, thereby effectively ameliorating hypertensive CR.

Optimizing the dosing regimen of roxadustat in kidney transplant recipients with early post-transplant anemia.

INTRODUCTION: Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen. METHODS: A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates. RESULTS: PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 µmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels. CONCLUSIONS: It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen.

TGF-ß1 and FOXM1 siRNA co-loaded nanoparticles by disulfide crosslinked PEG-PDMAEMA for the treatment of triple-negative breast cancer and its bone metastases in vitro.

INTRODUCTION: Triple-negative breast cancer (TNBC) is characterized by higher malignancy and mortality and is prone to distant metastasis, among which bone is the most common site. It's urgent to explore new strategies for the treatment of TNBC and its bone metastases. METHODS: A tumor environment responsive vector, poly-(dimethylaminoethyl methacrylate)-SS-poly(ethylene glycol)-SS-poly-(dimethylaminoethyl methacrylate) (PDMAEMA-SS-PEG-SS-PDMAEMA), was constructed to co-delivery transforming growth factor-ß1 (TGF-ß1) siRNA and forkhead box M1 (FOXM1) siRNA in MDA-MB-231 cells. The preparation, characterization, in vitro release, stability, and transfection efficiency of nanoparticles were measured. Cell viability, migration, and invasion of MDA-MB-231 cells were determined. Cell chemotactic migration and cell heterogeneity adhesion of MDA-MB-231 cells to the human osteoblast-like cell line MG-63 were determined. RESULTS: PDMAEMA-SS-PEG-SS-PDMAEMA self-assembled with siRNA at N/P of 15:1 into nanoparticles with a particle size of 122 nm. In vitro release exhibited redox and pH sensitivity, and the nanoparticles protected siRNA from degradation by RNase and serum protein, remaining stable at 4 °C with similar transfection efficiency with lipo2000. Nanoparticles co-loaded with TGF-ß1 siRNA and FOXM1 siRNA inhibited the cell viability, migration and invasion of MDA-MB-231 cells, as well as chemotactic migration and heterogeneous adhesion of MDA-MB-231 cells to MG-63 cells, showing a synergetic effect. After gene silencing on TGF-ß1 and FOXM1, the epithelial to mesenchymal transition (EMT) related molecules vimentin mRNA expression decreased while E-cadherin increased. CONCLUSIONS: PDMAEMA-SS-PEG-SS-PDMAEMA was suitable for TGF-ß1 siRNA and FOXM1 siRNA delivery, exhibiting a synergetic inhibition effect on TNBC and its bone metastases, which might be related to its synergetic inhibition on EMT.

Echinocystic acid inhibits sepsis-associated renal inflammation and apoptosis by targeting protein tyrosine phosphatase 1B.

Thefruits of Gleditsia sinensis Lam. have been utilized to treat inflammatory diseases in China. Echinocystic acid (EA), one pentacyclic triterpenoid isolated from thefruits of G. sinensis, exhibits an anti-inflammatory effect. However, its anti-sepsis activity and mechanism of action, especially the protective effect against sepsis-associated acute kidney injury (SA-AKI), are not investigated yet. This study is to explore the efficacy and potential mechanism of EA on SA-AKI. EA elevated the function of multiple organs and effectively reduced the increased inflammation and apoptosis of kidney tissue and HK-2 cells. DARTS, CETSA, and molecular docking experiments revealed that EA could directly bind to protein tyrosine phosphatase 1B (PTP1B), a widespread prototype non-receptor tyrosine phosphatase. Collectively, EA can alleviate murine SA-AKI though restraining inflammation and apoptosis and may be a potential natural drug for remedying SA-AKI.

Current practice, trends and attitudes of rheumatologists towards glucocorticoids use for rheumatoid arthritis (GURANTEE): a national cross-sectional survey across China.

INTRODUCTION: To investigate current practices, changes, and perceptions of rheumatologists regarding GC use in RA patients. METHODS: A cross-sectional survey was conducted using a structured questionnaire between April and August 2023. Rheumatologists from 31 province-level regions of Mainland China were invited to participate. Chi-squared tests were adopted to investigate the differences by sociodemographic characteristics. RESULTS: 1,717 rheumatologists from 598 hospitals completed the survey with a response rate of 92%. Up to 60% of participants expressed currently infrequent initiation of GC co-therapy with csDMARDs (hardly ever 7.0%; occasionally 24.6%; sometimes 29.1%), accompanied by a decline of frequency over time reported in 64.2%. Regarding attitudes towards bridging therapy with GC, 604 (35.2%) participants supported this approach, 468 (27.3%) opposed it, and 645 (37.6%) remained inconclusive. Time to GC discontinuation in context of csDMARDs was commonly reported within 6 months in current practice which has been narrowed over time. Reasons for chronic GC use were mostly reported due to suboptimal disease control, followed by the need of RA complications, and pre-existing comorbidities. After failure of GC cessation, majority of respondents (84.4%) would escalate RA therapy (commonly by addition of JAK inhibitors, TNF inhibitors), which usually or often facilitated the GC cessation. The most frequently reported advantages and weaknesses of GC were rapid and strong efficacy, adverse events, respectively. Regarding long-term low-dose GC use for RA, the percentage of respondents who supported, opposed, or depended on the situation were 15.9%, 17.2%, and 66.9%, respectively. CONCLUSIONS: The current data demonstrate that GC initiation for RA treatment is not as frequent as before and the awareness of GC discontinuation is growing in current practice. Attitudes towards GC co-therapy with csDMARDs vary considerably and long-term low-dose GC use remain situation dependent.

Leisure-time activities and disability among Chinese community-dwelling oldest old: evidence from the Chinese Longitudinal Healthy Longevity Study.

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults.

Aspects of Nickel, Cobalt and Lithium, the Three Key Elements for Li-Ion Batteries: An Overview on Resources, Demands, and Production.

With the booming of renewable clean energies towards reducing carbon emission, demands for lithium-ion batteries (LIBs) in applications to transportation vehicles and power stations are increasing exponentially. As a consequence, great pressures have been posed on the technological development and production of valuable elements key to LIBs, in addition to concerns about depletion of natural resources, environmental impacts, and management of waste batteries. In this paper, we compile recent information on lithium, nickel, and cobalt, the three most crucial elements utilized in LIBs, in terms of demands, current identified terrestrial resources, extraction technologies from primary natural resources and waste. Most nickel and cobalt are currently produced from high-grade sulfide ores via a pyrometallurgical approach. Increased demands have stimulated production of Ni and Co from low-grade laterites, which is commonly performed through the hydrometallurgical process. Most lithium exists in brines and is extracted via evaporation-precipitation in common industrial practice. It is noteworthy that at present, the pyrometallurgical process is energy-intensive and polluting in terms of gas emissions. Hydrometallurgical processes utilize large amounts of alkaline or acidic media in combination with reducing agents, generating hazardous waste streams. Traditional evaporation-precipitation consumes time, water, and land. Extraction of these elements from deep seas and recycling from waste are emerging as technologies. Advanced energy-saving and environmentally friendly processes are under extensive research and development and are crucial in the process of renewable clean energy implementation.

Causal Association between Circulating Metabolites and Dementia: A Mendelian Randomization Study.

The causal association of circulating metabolites with dementia remains uncertain. We assessed the causal association of circulating metabolites with dementia utilizing Mendelian randomization (MR) methods. We performed univariable MR analysis to evaluate the associations of 486 metabolites with dementia, Alzheimer's disease (AD), and vascular dementia (VaD) risk. For secondary validation, we replicated the analyses using an additional dataset with 123 metabolites. We observed 118 metabolites relevant to the risk of dementia, 59 of which were lipids, supporting the crucial role of lipids in dementia pathogenesis. After Bonferroni adjustment, we identified nine traits of HDL particles as potential causal mediators of dementia. Regarding dementia subtypes, protective effects were observed for epiandrosterone sulfate on AD (OR = 0.60, 95% CI: 0.48-0.75) and glycoproteins on VaD (OR = 0.89, 95% CI: 0.83-0.95). Bayesian model averaging MR (MR-BMA) analysis was further conducted to prioritize the predominant metabolites for dementia risk, which highlighted the mean diameter of HDL particles and the concentration of very large HDL particles as the predominant protective factors against dementia. Moreover, pathway analysis identified 17 significant and 2 shared metabolic pathways. These findings provide support for the identification of promising predictive biomarkers and therapeutic targets for dementia.

Ultrathin Ga2O3 Photodetector with Fast Response and Trajectory Tracking Capability Fabricated by Liquid Metal Oxidation.

Low-dimensional Ga2O3 demonstrates a unique ultraviolet photoresponse and could be used in various electronic and optical systems. However, the low-dimensional Ga2O3 photodetector is faced with the challenges of a complex preparation process and poor device performance. In this work, ultrathin Ga2O3 layers with ∼7 nm thickness are prepared on quartz rods by UV exposure to liquid gallium. Benefiting from low-density oxygen vacancy defects cured by UV exposure, the low-dimensional Ga2O3 photodetector exhibits a high response speed (rise: 64.7 µs; fall: 51.4 µs) and an exceptional linear dynamic range of 120 dB. Furthermore, the photodetector array based on these ultrathin Ga2O3 shows an effective trajectory tracking capability by monitoring UV source motion. This work develops a simple preparation method to construct a low-dimensional UV photodetector array with fast response and useful trajectory tracking capability, exhibiting the significance of ultrathin Ga2O3 in UV optoelectronics.

Transformer-based AI technology improves early ovarian cancer diagnosis using cfDNA methylation markers.

Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection.

Musical timbre style transfer with diffusion model.

In this work, we focus on solving the problem of timbre transfer in audio samples. The goal is to transfer the source audio's timbre from one instrument to another while retaining as much of the other musical elements as possible, including loudness, pitch, and melody. While image-to-image style transfer has been used for timbre and style transfer in music recording, the current state of the findings is unsatisfactory. Current timbre transfer models frequently contain samples with unrelated waveforms that affect the quality of the generated audio. The diffusion model has excellent performance in the field of image generation and can generate high-quality images. Inspired by it, we propose a kind of timbre transfer technology based on the diffusion model. To be specific, we first convert the original audio waveform into the constant-Q transform (CQT) spectrogram and adopt image-to-image conversion technology to achieve timbre transfer. Lastly, we reconstruct the produced CQT spectrogram into an audio waveform using the DiffWave model. In both many-to-many and one-to-one timbre transfer tasks, we assessed our model. The experimental results show that compared with the baseline model, the proposed model has good performance in one-to-one and many-to-many timbre transfer tasks, which is an interesting technical progress.

Development and validation of prognostic signatures of NAD+ metabolism and immune-related genes in colorectal cancer.

Background: Colorectal cancer (CRC) is a prevalent cause of death from malignant tumors. This study aimed to develop a nicotinamide adenine dinucleotide (NAD+) metabolism and immune-related prognostic signature, providing a theoretical foundation for prognosis and therapy in CRC patients. Methods: NAD + metabolism-related and immune-related subtypes of CRC patients were identified by consistent clustering. Differentially expressed genes (DEGs) between the two subtypes of CRC were identified by overlapping. A risk signature was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Independent prognostic predictors were authenticated by Cox analysis. Gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) were applied to investigate the connection between the prognostic signature and the immune microenvironment. Chemotherapy drug sensitivity and immunotherapy responsiveness were projected using the 'pRRophetic' package and Tumor Immune Dysfunction and Exclusion (TIDE) website. The Human Protein Atlas (HPA) database was used to assess the protein expression of prognostic genes in CRC and normal tissues. Results: Using bioinformatics methods, three prognostic genes related to immune-related NAD + metabolism were identified, and the results were used to establish and verify a prognostic signature related to immune-related NAD + metabolism in CRC patients. Cox regression analysis confirmed that the risk score was a reliable independent prognostic predictor. GSVA and ssGSEA indicated that the prognostic signature was associated with the immune microenvironment. TIDE analysis suggested that the signature might act as an immunotherapy predictor. Chemotherapy sensitivity analysis revealed that COMP was correlated with chemotherapy sensitivity in CRC patients and might be a potential therapeutic target. Conclusion: This study identified NAD + metabolism-immune-related prognostic genes (MOGAT2, COMP, and DNASE1L3) and developed a prognostic signature for CRC prognosis, which is significant for clinical prognosis prediction and treatment strategy decisions for CRC patients.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

Cross-Priming-Linked Hierarchical Isothermal Amplification Programming Progressive Activating Clustered Regularly Interspaced Short Palindromic Repeats/Cas12a in miRNA Signaling.

Cascade isothermal nucleic acid amplification, which integrates several different amplification protocols to enhance the assay performance, is widely utilized in biosensing, particularly for detecting microRNAs (miRNAs), crucial biomarkers associated with tumor initiation and progression. However, striking a balance between a high amplification efficiency and simplicity in design remains a challenge. Therefore, methods achieving high amplification efficiency without significantly increasing complexity are highly favored. In this study, we propose a novel approach for miRNA detection, employing cross-priming-linked hierarchical isothermal amplification (CP-HIA) to progressively activate the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system. The CP-HIA method strategically combines nicking-rolling circle amplification (n-RCA) and palindrome-aided circular strand displacement amplification (p-CSDA) for miRNA detection. Remarkably, this method utilizes only two main probes. Its key innovation lies in the interactive cross-priming strategy, wherein the amplification product from n-RCA is recycled to further drive p-CSDA, and vice versa. This interactive process establishes a hierarchical amplification, significantly enriching the activation probes for progressive CRISPR/Cas12a activation and subsequent target signal amplification. Consequently, the method exhibits greatly enhanced analytical performance, including high sensitivity and specificity in detecting low concentrations of miRNA. As low as 1.06 fM miRNA can thus be quantitatively detected, and the linear response of the miRNA is from 10 fM to 10 nM. These features demonstrate its potential for early disease diagnosis and monitoring. We anticipate that the CP-HIA method will serve as a promising platform for developing advanced molecular diagnostic tools for biomedical research.

Pd/Cu Dual Metal-Catalyzed Regioselective [2 + 2 + 2] Cycloaddition of Malononitriles with Alkynes to Densely Substituted Pyridines.

Transition metal-catalyzed [2 + 2 + 2] cycloaddition of nitriles and two alkynes is an efficient method for assembling pyridines. However, examples employing palladium catalysis have rarely been disclosed, and the processes of reactivity and selectivity remain unclear. We report here a palladium/copper dual metal-catalyzed [2 + 2 + 2] cycloaddition of diynyl-tethered malononitriles and terminal alkynes to synthesize densely substituted pyridines. This method features a good substrate scope, synthetically useful yields, and perfect regioselectivity. The derivatization of the pyridine products demonstrates the potential application of this method in synthesizing heterocycles and as ligands in photocatalysis. Preliminary mechanistic studies suggest that the reaction undergoes aza-oxidative cycloaddition of Pd(0) with nitrile and alkyne, followed by alkyne insertion and reductive elimination. The presence of copper is crucial to its reactivity and regioselectivity.

Ovarian stimulation response and fertility outcomes in patients with breast cancer across different stages, grades, and hormone receptor status for fertility preservation.

BACKGROUND: This study aimed to explore the potential impact of stage, grade, and hormone receptor profile on ovarian stimulation response and fertility preservation outcomes. METHODS: This retrospective cohort study evaluated data from breast cancer patients who underwent fertility preservation at a tertiary medical center between 2014 and 2022. The outcomes of women with low-stage cancer (stages I and II) were compared with those of women with high-stage disease (stages III and IV or lymph node metastasis). Similarly, we compared those with low-grade (grades 1 and 2) and high-grade (grade 3) malignancies. In addition, we compared different hormone statuses of breast cancer (1) estrogen receptor (ER) positive vs. ER-negative and (2) triple-negative breast cancer (TNBC) vs. non-TNBC. The primary outcome measured was the number of mature oocytes, while the secondary outcomes included the numbers of total oocytes retrieved, peak estradiol levels, and subsequent fertility preservation outcomes. RESULTS: A total of 47 patients were included. Patients with high-grade tumors had a comparable number of mature oocytes (8 vs. 10, p = 0.08) compared to patients with low grade cancers. The stage-based analysis revealed a similar number of mature oocytes (8 vs. 10, p = 0.33) between high/low stage patients. In the hormone receptor-based analysis, no differences were seen in mature oocytes collected between the ER-positive/ER-negative group (9 vs. 9, p = 0.87) and the TNBC/non-TNBC group (11 vs. 9, p = 0.13). The utilization rate was 27.6% (13/47). CONCLUSION: Our study showed similar ovarian stimulation response and fertility preservation outcomes among breast cancer patients with different prognostic factors.

Five-Surface Phosphor-in-Glass for Enhanced Illumination and Superior Color Uniformity in Large-View Scale LEDs.

A novel five-surface phosphor-in-glass (FS-PiG) structure for high illumination and excellent color uniformity in large-view scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y3Al5O12:Ce3+) was uniformly mixed with ceramic and sintered at 680 °C to form a phosphor wafer. Sophisticated laser engraving was employed on the phosphor wafer to form saddle-shaped large-view scale FS-PiG LEDs. The performance of the FS-PiG LEDs exhibited an illumination of 401 lm, average color temperature (CCT) of 5488 K ± 110 K, and color coordinates (CIE) of (0.3179 ± 0.003, 0.3352 ± 0.003). In contrast to convention single-surface phosphor-in-glass (SS-PiG) LEDs, the performance exhibited an illumination of 380 lm, average CCT of 5830 K ± 758 K, and CIE of (0.3083 ± 0.07, 0.3172 ± 0.07). These indicated that the performance of the FS-PiG LEDs was higher than the SS-PiG LEDs for illumination, CCT, and CIE by 1.7, 7, and 23 times, respectively. Furthermore, the FS-PiG LEDs demonstrate a lower lumen loss of 2% and a reduced chromaticity shift of 5.4 × 10-3 under accelerated aging at 350 °C for 1008 h, owing to the high ceramic melting temperature of up to 510 °C. In this study, the proposed FS-PiG large-view scale LEDs with excellent optical performance and high reliability may be promising candidates to replace the conventional phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

Physiological and Transcriptome Responses of Sweet Potato [Ipomoea batatas (L.) Lam] to Weak-Light Stress.

In the relay intercropping system of maize/sweet potato, the growth of the sweet potatoes is seriously limited by weak light stress in the early stage due to shade from maize plants. However, it is not clear how the weak light affects sweet potatoes and causes tuberous root loss. By setting two light intensity levels (weak light = 30% transmittance of normal light), this study evaluated the responses of two sweet potato cultivars with different tolerances to weak light in a field-based experiment and examined the divergence of gene expression related to light and photosynthesis in a pot-based experiment. The results showed that under weak light, the anatomic structure of functional leaves changed, and the leaf thickness decreased by 39.98% and 17.32% for Yuhongxinshu-4 and Wanshu-7, respectively. The ratio of S/R increased, and root length, root superficial area, and root volume all decreased. The photosynthetic enzyme rubisco was weakened, and the net photosynthetic rate (Pn) declined as well. The level of gene expression in Wanshu-7 was higher than that of Yuhongxinshu-4. The KEGG analysis showed that differentially expressed genes from the two cultivars under weak-light stress used the same enrichment pathway, mainly via glutathione metabolism and flavonoid biosynthesis. After full light levels were restored, the differentially expressed genes were all enriched in pathways such as photosynthesis, photosynthetic pigment synthesis, and carbon metabolism. These findings indicated that weak light changed the plant morphology, photosynthetic physiology and gene expression levels of sweet potatoes, which eventually caused losses in the tuberous root yield. The more light-sensitive cultivar (Wanshu-7) had stronger reactions to weak light. This study provides a theoretical basis and strategy for breeding low-light-tolerant varieties and improving relay intercropping production in sweet potatoes.

Hyperhomocysteine promotes cataract development through mTOR-mediated inhibition of autophagy and connexins expression.

AIM: Hyperhomocysteine has been recognized as an independent risk factor of multiple diseases, including several eye diseases. In this study, we aim to investigate whether increased homocysteine (Hcy) is related to cataracts, and to explore whether dysregulation of mTOR-mediated autophagy and connexin expression are underlying mechanisms. METHOD: We first developed a method of liquid chromatography tandem mass spectrometry to accurately measure serum concentrations of Hcy in 287 cataract patients and 334 healthy controls. Next, we treated human lens epithelial (HLC-B3) cells with Hcy at different concentrations and durations, and then analyzed expression of autophagy-related markers and connexins, as well as phosphorylated mTOR (p-mTOR) in these cells by Western blotting. Formation of autophagic vacuoles and intracellular Ca2+ in the Hcy-treated cells were observed by fluorescence microscopy. Further, we performed a rescue experiment in the Hcy-treated HLC-B3 cells by pre-incubation with rapamycin, an mTOR inhibitor. RESULTS: The serum levels of Hcy in patients with cataracts were significantly increased compared to those in healthy controls. In cultured HLC-B3 cells, expression of autophagy related markers (LC3B and Beclin1) and connexins (Cx43 and Cx50) was inhibited by Hcy treatment in a dose- and duration-dependent manner. Accumulation of Ca2+ in the Hcy-treated lens epithelial cells was observed as a consequence of reduced connexin expression. Meanwhile, expression of p-mTOR increased, representing up-regulation of the mTOR pathway. Importantly, inhibition of autophagy and connexin expression due to hyperhomocysteine was rescued via mTOR suppression by pretreatment with rapamycin in HLC-B3 cells. CONCLUSION: Our results demonstrate that hyperhomocysteine might promote cataract development through two mTOR-mediated pathways in the lens epithelial cells: 1) dysregulation of autophagy and 2) accumulation of intracellular calcium via decreased connexin expression.

Treatment of Parkinson's disease model with human umbilical cord mesenchymal stem cell-derived exosomes loaded with BDNF.

AIMS: Parkinson's disease (PD) is a common neurodegenerative disease that has received widespread attention; however, current clinical treatments can only relieve its symptoms, and do not effectively protect dopaminergic neurons. The purpose of the present study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived exosomes loaded with brain-derived neurotrophic factor (BDNF-EXO) on PD models and to explore the underlying mechanisms of these effects. MAIN METHODS: 6-Hydroxydopamine was used to establish in vivo and in vitro PD models. Western blotting, flow cytometry, and immunofluorescence were used to detect the effects of BDNF-EXO on apoptosis and ferroptosis in SH-SY5Y cells. The in vivo biological distribution of BDNF-EXO was detected using a small animal imaging system, and dopaminergic neuron improvements in brain tissue were detected using western blotting, immunofluorescence, immunohistochemistry, and Nissl and Prussian blue staining. KEY FINDINGS: BDNF-EXO effectively suppressed 6-hydroxydopamine-induced apoptosis and ferroptosis in SH-SY5Y cells. Following intravenous administration, BDNF-EXO crossed the blood-brain barrier to reach afflicted brain regions in mice, leading to a notable enhancement in neuronal survival. Furthermore, BDNF-EXO modulated microtubule-associated protein 2 and phosphorylated tau expression, thereby promoting neuronal cytoskeletal stability. Additionally, BDNF-EXO bolstered cellular antioxidant defense mechanisms through the activation of the nuclear factor erythroid 2-related factor 2 signaling pathway, thereby conferring neuroprotection against damage. SIGNIFICANCE: The novel drug delivery system, BDNF-EXO, had substantial therapeutic effects in both in vivo and in vitro PD models, and may represent a new treatment strategy for PD.