Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Z-scheme heterojunction g-C3N4-TiO2 reinforced chitosan/poly(vinyl alcohol) film: Efficient and recyclable for fruit packaging.

Nanoparticles-loaded bio-based polymers have emerged as a sustainable substitute to traditional oil-based packaging materials, addressing the challenges of limited recyclability and significant environmental impact. However, the functionality and efficiency of nanoparticles have a significant impact on the application of bio-based composite films. Herein, graphitic carbon nitride (g-C3N4) and titanium dioxide (TiO2) coupled photocatalyst (g-C3N4-TiO2) was prepared by one-step calcination and introduced into chitosan (CS) and polyvinyl alcohol (PVA) solution to fabricate g-C3N4-TiO2/CS/PVA green renewable composite film via solution casting method. The results demonstrated the successful preparation of a Z-scheme heterojunction g-C3N4-TiO2 with exceptional photocatalytic activity. Furthermore, the incorporation of heterojunction enhanced mechanical properties, water barrier, and ultraviolet (UV) resistance properties of the fresh-keeping film. The g-C3N4-TiO2/CS/PVA composite film exhibited superior photocatalytic antibacterial preservation efficacy on strawberries under LED light, with a prolonged preservation time of up to 120 h, when compared to other films such as polyethylene (PE), CS/PVA, g-C3N4/CS/PVA, and TiO2/CS/PVA. In addition, the composite film has good recyclability and renewability. This work is expected to have great potential for low-cost fruit preservation and sustainable packaging, which also contributes to environmental protection.

Study on the Effect of Different Concentrations of SO2 on the Volatile Aroma Components of 'Beibinghong' Ice Wine.

SO2 plays an important role in wine fermentation, and its effects on wine aroma are complex and diverse. In order to investigate the effects of different SO2 additions on the fermentation process, quality, and flavor of 'Beibinghong' ice wine, we fermented 'Beibinghong' picked in 2019. We examined the fermentation rate, basic physicochemical properties, and volatile aroma compound concentrations of 'Beibinghong' ice wine under different SO2 additions and constructed a fingerprint of volatile compounds in ice wine. The results showed that 44 typical volatile compounds in 'Beibinghong' ice wine were identified and quantified. The OAV and VIP values were calculated using the threshold values of each volatile compound, and t the effect of SO2 on the volatile compounds of 'Beibinghong' ice wine might be related to five aroma compounds: ethyl butyrate, ethyl propionate, ethyl 3-methyl butyrate-M, ethyl 3-methyl butyrate-D, and 3-methyl butyraldehyde. Tasting of 'Beibinghong' ice wine at different SO2 additions revealed that the overall flavor of 'Beibinghong' ice wine was the highest at an SO2 addition level of 30 mg/L. An SO2 addition level of 30 mg/L was the optimal addition level. The results of this study are of great significance for understanding the effect of SO2 on the fermentation of 'Beibinghong' ice wine.

A Fusion Network with Stacked Denoise Autoencoder and Meta Learning for Lateral Walking Gait Phase Recognition and Multi-Step-Ahead Prediction.

Lateral walking gait phase recognition and prediction are the premise of hip exoskeleton application in lateral resistance walk exercise. In this work, we presented a fusion network with stacked denoise autoencoder and meta learning (SDA-NN-ML) to recognize gait phase and predict gait percentage from IMU signals. Experiments were conducted to detect the four lateral walking gait phases and predict their percentage in 10 healthy subjects across different speeds. The performance of SDA-NN-ML and other widely used algorithms including Support Vector Machine (SVM), Adaptive Boosting (AdaBoost) and Long Short Term Memory (LSTM) were evaluated. The cross-subject recognition accuracy of SDA-NN-ML (89.94%) decreased by 4.62% compared to the training accuracy, which outperformed SVM (8.60%), AdaBoost (5.61%), and LSTM (7.12%). For real-time and cross-subject prediction of gait phase percentage, the RMSE of SDA-NN-ML (0.2043) outperformed that of a single regression network (0.2426). With a signal noise ratio of 100:30, the cross-subject recognition accuracy decreased by a mere 5.70%, while the prediction result (RMSE) of SDA-NN-ML increased by 0.0167 when compared to the noise-free results. SDA-NN-ML demonstrates a stable multi-step-ahead prediction ability with an accuracy higher than 82.50% and an RMSE of less than 0.23 when the ahead time is less than 200 ms. The results demonstrated that the proposed method has high accuracy and robust performance in lateral walking gait recognition and prediction.

Analysis of Quality Differences in Radix Dipsaci before and after Processing with Salt Based on Quantitative Control of HPLC Multi-Indicator Components Combined with Chemometrics.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.

Genome-Wide Identification and Expression Analyses of the FAR1/FHY3 Gene Family Provide Insight into Inflorescence Development in Maize.

As transcription factors derived from transposase, FAR-RED IMPAIRED RESPONSE1 (FAR1) and its homolog FHY3 play crucial roles in the regulation of light signaling and various stress responses by coordinating the expression of downstream target genes. Despite the extensive investigation of the FAR1/FHY3 family in Arabidopsis thaliana and other species, a comprehensive examination of these genes in maize has not been conducted thus far. In this study, we employed a genomic mining approach to identify 16 ZmFAR1 genes in the maize inbred line B73, which were further classified into five subgroups based on their phylogenetic relationships. The present study characterized the predicted polypeptide sequences, molecular weights, isoelectric points, chromosomal distribution, gene structure, conserved motifs, subcellular localizations, phylogenetic relationships, and cis-regulatory elements of all members belonging to the ZmFAR1 family. Furthermore, the tissue-specific expression of the 16 ZmFAR1 genes was analyzed using RNA-seq, and their expression patterns under far-red light conditions were validated in the ear and tassel through qRT-qPCR. The observed highly temporal and spatial expression patterns of these ZmFAR1 genes were likely associated with their specific functional capabilities under different light conditions. Further analysis revealed that six ZmFAR1 genes (ZmFAR1-1, ZmFAR1-10, ZmFAR1-11, ZmFAR1-12, ZmFAR1-14, and ZmFAR1-15) exhibited a response to simulated shading treatment and actively contributed to the development of maize ears. Through the integration of expression quantitative trait loci (eQTL) analyses and population genetics, we identified the presence of potential causal variations in ZmFAR1-14 and ZmFAR1-9, which play a crucial role in regulating the kernel row number and kernel volume weight, respectively. In summary, this study represents the initial identification and characterization of ZmFAR1 family members in maize, uncovering the functional variation in candidate regulatory genes associated with the improvement of significant agronomic traits during modern maize breeding.

Degradation and mechanism of PFOA by peroxymonosulfate activated by nitrogen-doped carbon foam-anchored nZVI in aqueous solutions.

Perfluorooctanoic acid (PFOA) is an emerging pollutant that is non-biodegradable and presents severe environmental and human health risks. In this study, we present an effective and mild approach for PFOA degradation that involves the use of nitrogen-doped carbon foam anchored with nanoscale zero-valent iron (nZVI@NCF) to activate low concentration peroxymonosulfate (PMS) for the treatment. The nZVI@NCF/PMS system efficiently removed 84.4% of PFOA (2.4 µM). The active sites of nZVI@NCF including Fe0 (110) and graphitic nitrogen played crucial roles in the degradation. Electrochemical analyses and density functional theory calculations revealed that nZVI@NCF acted as an electronic donor, transferring electrons to both PMS and PFOA during the reaction. By further analyzing the electron paramagnetic resonance and byproducts, it was determined that electron transfer and singlet oxygen were responsible for PFOA degradation. Three degradation pathways involving decarboxylation and surface reduction of PFOA in the nZVI@NCF/PMS system were determined. Finding from this study indicate that nZVI@NCF/PMS systems are effective in degrading PFOA and thus present a promising persulfate-advanced oxidation process technology for PFAS treatment.

Diversity of Endophytes of Actinidia arguta in Different Seasons.

The seasonal changes in environmental conditions can alter the growth states of host plants, thereby affecting the living environment of endophytes and forming different endophytic communities. This study employs Illumina MiSeq next-generation sequencing to analyze the 16SrRNA and ITS rDNA of endophytes in 24 samples of Actinidia arguta stem tissues across different seasons. The results revealed a high richness and diversity of endophytes in Actinidia arguta, with significant seasonal variations in microbial community richness. This study identified 897 genera across 36 phyla for bacteria and 251 genera across 8 phyla for fungi. Notably, 69 bacterial genera and 19 fungal genera significantly contributed to the differences in community structure across seasons. A distinctive feature of coexistence in the endophytic community, both specific and conservative across different seasons, was observed. The bacterial community in winter demonstrated significantly higher richness and diversity compared to the other seasons. Environmental factors likely influence the optimal timing for endophyte colonization. Solar radiation, temperature, precipitation, and relative humidity significantly impact the diversity of endophytic bacteria and fungi. In addition, seasonal variations show significant differences in the nutritional modes of fungal endophytes and the degradation, ligninolysis, and ureolysis functions of bacterial endophytes. This study elucidates the potential role of endophytes in assisting Actinidia arguta in adapting to seasonal changes and provides a theoretical basis for further exploration of functional microbial strains.

ZmELF3.1 integrates the RA2-TSH4 module to repress maize tassel branching.

Tassel branch number (TBN) is a key agronomic trait for adapting to high-density planting and grain yield in maize. However, the molecular regulatory mechanisms underlying tassel branching are still largely unknown. Here, we used molecular and genetic studies together to show that ZmELF3.1 plays a critical role in regulating TBN in maize. Previous studies showed that ZmELF3.1 forms the evening complex through interacting with ZmELF4 and ZmLUX to regulate flowering in maize and that RA2 and TSH4 (ZmSBP2) suppresses and promotes TBN in maize, respectively. In this study, we show that loss-of-function mutants of ZmELF3.1 exhibit a significant increase of TBN. We also show that RA2 directly binds to the promoter of TSH4 and represses its expression, thus leading to reduced TBN. We further demonstrate that ZmELF3.1 directly interacts with both RA2 and ZmELF4.2 to form tri-protein complexes that further enhance the binding of RA2 to the promoter of TSH4, leading to suppressed TSH4 expression and consequently decreased TBN. Our combined results establish a novel functional link between the ELF3-ELF4-RA2 complex and miR156-SPL regulatory module in regulating tassel branching and provide a valuable target for genetic improvement of tassel branching in maize.

Shen Qi Wan ameliorates nephritis in chronic kidney disease via AQP1 and DEFB1 regulation.

Shen Qi Wan (SQW) has been proven to exert anti-inflammatory effects in the kidneys of CKD models accompanied by unclear therapeutic mechanisms. This study aims to evaluate the kidney-protective and anti-inflammatory effects of SQW and to elucidate its fundamental mechanisms for CKD treatment. Firstly, the main active components of SQW were identified by UPLC-Q-TOF/MS technique. Subsequently, we evaluated inflammatory factors, renal function and renal pathology changes following SQW treatment utilizing adenine-induced CKD mice and aquaporin 1 knockout (AQP1-/-) mice. Additionally, we conducted RNA-seq analysis and bioinformatics analysis to predict the SQW potential therapeutic targets and anti-nephritis pathways. Simultaneously, WGCNA analysis method and machine learning algorithms were used to perform a clinical prognostic analysis of potential biomarkers in CKD patients from the GEO database and validated through clinical samples. Lipopolysaccharide-induced HK-2 cells were further used to explore the mechanism. We found that renal collagen deposition was reduced, serum inflammatory cytokine levels decreased, and renal function was improved after SQW intervention. It can be inferred that ß-defensin 1 (DEFB1) may be a pivotal target, as confirmed by serum and renal tissue samples from CKD patients. Furthermore, SQW assuages inflammatory responses by fostering AQP1-mediated DEFB1 expression was confirmed in in vitro and in vivo studies. Significantly, the renal-protective effect of SQW is to some extent attenuated after AQP1 gene knockout. SQW could reduce inflammatory responses by modulating AQP1 and DEFB1. These findings underscore the potential of SQW as a promising contender for novel prevention and treatment strategies within the ambit of CKD management.

Characterization of Key Compounds of Organic Acids and Aroma Volatiles in Fruits of Different Actinidia argute Resources Based on High-Performance Liquid Chromatography (HPLC) and Headspace Gas Chromatography-Ion Mobility Spectrometry (HS-GC-IMS).

Actinidia arguta, known for its distinctive flavor and high nutritional value, has seen an increase in cultivation and variety identification. However, the characterization of its volatile aroma compounds remains limited. This study aimed to understand the flavor quality and key volatile aroma compounds of different A. arguta fruits. We examined 35 A. arguta resource fruits for soluble sugars, titratable acids, and sugar-acid ratios. Their organic acids and volatile aroma compounds were analyzed using high-performance liquid chromatography (HPLC) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). The study found that among the 35 samples tested, S12 had a higher sugar-acid ratio due to its higher sugar content despite having a high titratable acid content, making its fruit flavor superior to other sources. The A. arguta resource fruits can be classified into two types: those dominated by citric acid and those dominated by quinic acid. The analysis identified a total of 76 volatile aroma substances in 35 A. arguta resource fruits. These included 18 esters, 14 alcohols, 16 ketones, 12 aldehydes, seven terpenes, three pyrazines, two furans, two acids, and two other compounds. Aldehydes had the highest relative content of total volatile compounds. Using the orthogonal partial least squares discriminant method (OPLS-DA) analysis, with the 76 volatile aroma substances as dependent variables and different soft date kiwifruit resources as independent variables, 33 volatile aroma substances with variable importance in projection (VIP) greater than 1 were identified as the main aroma substances of A. arguta resource fruits. The volatile aroma compounds with VIP values greater than 1 were analyzed for odor activity value (OAV). The OAV values of isoamyl acetate, 3-methyl-1-butanol, 1-hexanol, and butanal were significantly higher than those of the other compounds. This suggests that these four volatile compounds contribute more to the overall aroma of A. arguta. This study is significant for understanding the differences between the fruit aromas of different A. arguta resources and for scientifically recognizing the characteristic compounds of the fruit aromas of different A. arguta resources.

Microring structure for flexible polymer waveguide-based optical pressure sensing.

Flexible pressure sensors provide a promising platform for artificial smart skins, and photonic devices provide a new technique to fabricate pressure sensors. Here, we present a flexible waveguide-based optical pressure sensor based on a microring structure. The waveguide-based optical pressure sensor is based on a five-cascade microring array structure with a size of 1500 µm × 500 µm and uses the change in output power to linearly characterize the change in pressure acting on the device. The results show that the device has a sensing range of 0-60 kPa with a sensitivity of 23.14 µW/kPa, as well as the ability to detect pulse signals, swallowing, hand gestures, etc. The waveguide-based pressure sensors offer the advantages of good output linearity, high integration density and easy-to-build arrays.

Electroacupuncture at ST36 acupoint regulates stem cells during experimental autoimmune encephalomyelitis.

BACKGROUND: Electroacupuncture (EA) is given to assist in the treatment of MS, which is an effective therapeutic method. However, the therapy mechanism of EA related to stem cells in the treatment of MS is not yet known. In this study, we used a classic animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) to evaluate the therapeutic effect of EA at Zusanli (ST36) acupoint in EAE and shed light on its potential roles in the effects of stem cells in vivo. METHODS: The EAE animal models were established. From the first day after immunization, EAE model mice received EA at ST36 acupoint, named the EA group. The weight and clinical score of the three groups were recorded for 28 days. The demyelination, inflammatory cell infiltration, and markers of neural stem cells (NSCs), hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs) were compared. RESULTS: We showed that EAE mice treated with EA at ST36 acupoint, were suppressed in demyelination and inflammatory cell infiltration, and thus decreased clinical score and weight loss and mitigated the development of EAE when compared with the EAE group. Moreover, our data revealed that the proportions of NSCs, HSCs, and MSCs increased in the EA group compared with the EAE group. CONCLUSIONS: Our study suggested that EA at ST36 acupoint was an effective nonpharmacological therapeutic protocol that not only reduced the CNS demyelination and inflammatory cell infiltration in EAE disease but also increased the proportions of various stem cells. Further study is necessary to better understand how EA at the ST36 acupoint affects EAE.

Unraveling Prevalence and Effects of Deleterious Mutations in Maize Elite Lines across Decades of Modern Breeding.

Future breeding is likely to involve the detection and removal of deleterious alleles, which are mutations that negatively affect crop fitness. However, little is known about the prevalence of such mutations and their effects on phenotypic traits in the context of modern crop breeding. To address this, we examined the number and frequency of deleterious mutations in 350 elite maize inbred lines developed over the past few decades in China and the United States. Our findings reveal an accumulation of weakly deleterious mutations and a decrease in strongly deleterious mutations, indicating the dominant effects of genetic drift and purifying selection for the two types of mutations, respectively. We also discovered that slightly deleterious mutations, when at lower frequencies, were more likely to be heterozygous in the developed hybrids. This is consistent with complementation as a potential explanation for heterosis. Subsequently, we found that deleterious mutations accounted for more of the variation in phenotypic traits than nondeleterious mutations with matched minor allele frequencies, especially for traits related to leaf angle and flowering time. Moreover, we detected fewer deleterious mutations in the promoter and gene body regions of differentially expressed genes across breeding eras than in nondifferentially expressed genes. Overall, our results provide a comprehensive assessment of the prevalence and impact of deleterious mutations in modern maize breeding and establish a useful baseline for future maize improvement efforts.

Global proteome and lysine succinylation analyses provide insights into the secondary metabolism in Salvia miltiorrhiza.

Danshen, belongs to the Lamiaceae family, and its scientific name is Salvia miltiorrhiza Bunge. It is a valuable medicinal plant to prevent and treat cardiovascular and cerebrovascular diseases. Lysine succinylation, a widespread modification found in various organisms, plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. Our findings reveal 566 lysine succinylation sites in 348 protein sequences. We observed 110 succinylated proteins related to secondary metabolism, totaling 210 modification sites. Our analysis identified 53 types of enzymes among the succinylated proteins, including phenylalanine ammonia-lyase (PAL) and aldehyde dehydrogenase (ALDH). PAL, a crucial enzyme involved in the biosynthesis of rosmarinic acid and flavonoids, displayed succinylation at two sites. ALDH, which participates in the phenylpropane metabolic pathway, was succinylated at 8 eight sites. These observations suggest that lysine succinylation may play a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on plant succinylation, specifically as a reference point. SIGNIFICANCE: Salvia miltiorrhiza Bunge is a valuable medicinal plant that prevents and treats cardiovascular and cerebrovascular diseases. Lysine succinylation plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. These observations suggest that lysine succinylation may act as a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on succinylation in plants, specifically as a reference point.

Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-ß1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-ß1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer's disease.

BACKGROUND: Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summarize the mechanisms through which ICA treats AD. METHODS: The PubMed and CNKI databases were utilized to review the advancements in ICA's role in AD prevention and treatment by analyzing literature published between January 2005 and April 2023. To further illustrate ICA's impact on AD development, tables, and images are included to summarize the relationships between various mechanisms. RESULTS: The study reveals that ICA ameliorates cognitive deficits in AD model mice by modulating Aß via multiple pathways, including BACE-1, NO/cGMP, Wnt/Ca2+, and PI3K/Akt signaling. ICA exhibits neuroprotective properties by inhibiting neuronal apoptosis through the suppression of ER stress in AD mice, potentially linked to NF-κB, MAPK, ERK, and PERK/Eif2α signaling pathways. Moreover, ICA may safeguard neurons by attenuating mitochondrial oxidative stress injury. ICA can also enhance learning, memory, and cognition by improving synaptic structure via regulation of the PSD-95 protein. Furthermore, ICA can mitigate neuroinflammation by inactivating microglial activity through the upregulation of PPARγ, TAK1/IKK/NF-κB, and JNK/p38 MAPK signaling pathways. CONCLUSION: This study indicates that ICA possesses multiple beneficial effects in AD treatment. Through the integration of pharmacological and molecular biological research, ICA may emerge as a promising candidate to expedite the advancement of TCM in the clinical management of AD.

Gene expression and expression quantitative trait loci analyses uncover natural variations underlying the improvement of important agronomic traits during modern maize breeding.

Maize (Zea mays L.) is a major staple crop worldwide, and during modern maize breeding, cultivars with increased tolerance to high-density planting and higher yield per plant have contributed significantly to the increased yield per unit land area. Systematically identifying key agronomic traits and their associated genomic changes during modern maize breeding remains a significant challenge because of the complexity of genetic regulation and the interactions of the various agronomic traits, with most of them being controlled by numerous small-effect quantitative trait loci (QTLs). Here, we performed phenotypic and gene expression analyses for a set of 137 elite inbred lines of maize from different breeding eras in China. We found four yield-related traits are significantly improved during modern maize breeding. Through gene-clustering analyses, we identified four groups of expressed genes with distinct trends of expression pattern change across the historical breeding eras. In combination with weighted gene co-expression network analysis, we identified several candidate genes regulating various plant architecture- and yield-related agronomic traits, such as ZmARF16, ZmARF34, ZmTCP40, ZmPIN7, ZmPYL10, ZmJMJ10, ZmARF1, ZmSWEET15b, ZmGLN6 and Zm00001d019150. Further, by combining expression quantitative trait loci (eQTLs) analyses, correlation coefficient analyses and population genetics, we identified a set of candidate genes that might have been under selection and contributed to the genetic improvement of various agronomic traits during modern maize breeding, including a number of known key regulators of plant architecture, flowering time and yield-related traits, such as ZmPIF3.3, ZAG1, ZFL2 and ZmBES1. Lastly, we validated the functional variations in GL15, ZmPHYB2 and ZmPYL10 that influence kernel row number, flowering time, plant height and ear height, respectively. Our results demonstrates the effectiveness of our combined approaches for uncovering key candidate regulatory genes and functional variation underlying the improvement of important agronomic traits during modern maize breeding, and provide a valuable genetic resource for the molecular breeding of maize cultivars with tolerance for high-density planting.

Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. AIM OF THE STUDY: The purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR. MATERIALS AND METHODS: The model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-α), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS. RESULTS: The results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-α were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified. CONCLUSION: This study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed.

Pan-Cancer Analysis Reveals PPRC1 as a Novel Prognostic Biomarker in Ovarian Cancer and Hepatocellular Carcinoma.

Background and Objectives: As is well understood, peroxisome proliferator-activated receptor gamma cofactor-related 1 (PPRC1) plays a central role in the transcriptional control of the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) process, yet its critical role in pan-cancer remains unclear. Materials and Methods: In this paper, the expression levels of PPRC1 in different tumor tissues and corresponding adjacent normal tissues were analyzed based on four databases: The Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), and Tumor Immune Estimation Resource (TIMER). Meanwhile, the prognostic value of PPRC1 was inferred using Kaplan-Meier plotter and forest-plot studies. In addition, the correlation between PPRC1 expression and tumor immune cell infiltration, immune checkpoints, and the tumor-stemness index was analyzed using TCGA and TIMER databases. Results: According to our findings, the expression level of PPRC1 was found to be different in different cancer types and there was a positive correlation between PPRC1 expression and prognosis in several tumor types. In addition, PPRC1 expression was found to be significantly correlated with immune cell infiltration, immune checkpoints, and the tumor-stemness index in both ovarian and hepatocellular carcinoma. Conclusions: PPRC1 demonstrated promising potential as a novel biomarker in pan-cancer due to its potential association with immune cell infiltration, expression of immune checkpoints, and the tumor-stemness index.