ABSTRACT
Lonicera japonica Flos is a valuable herb in the Lonicerae family. While transcriptomic studies on L. japonica have focused on different tissues (stems, leaves, flowers) or flowering stages, few have investigated the molecular mechanisms underlying chemical composition synthesis influenced by exogenous factors, such as foliar fertilization. Moreover, most transcriptomic studies on L. Japonica have been conducted on chlorogenic acid and luteoloside, and the molecular synthesis mechanism of the overall chemical composition has not been analyzed. Methods: We conducted a single-factor, four-level foliar fertilization experiment using yeast polysaccharides. Different yeast polysaccharides concentrations were sprayed on L. japonica for six consecutive days with dynamic sampling. High-performance liquid chromatography determined the active ingredients in each group. The two groups exhibiting the most significant differences were selected for transcriptomic analysis to identify key synthetic genes responsible for L. japonica's active ingredients. Key results: Principal component analysis conducted on samples collected on September 8 revealed significant differences in the active ingredient amounts between the 0.1 g/L yeast polysaccharides treatment group and the control group. Transcriptome sequencing analysis identified 218 significantly differentially expressed genes, including 60 upregulated and 158 downregulated genes. Twelve differential genes involved in the chemical components synthesis pathway of L. japonica under yeast polysaccharides treatment were identified: PAL1, PAL2, PAL3, 4CL1, 4CL, CHS1, CHS2, CHS, CHI1, CHI2, F3H, and SOH. Conclusions: This study contributes to the theoretical understanding of essential synthetic genes associated with L. japonica's active ingredients. It offers data support for further gene exploration and sheds light on the molecular mechanisms underlying L. japonica quality formation. These findings hold significant implications for enhancing the content of secondary metabolites of L. japonica. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01482-1.
ABSTRACT
OBJECTIVE: Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established although both have demonstrated potential in gastrointestinal diseases. The aim of the current study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children. METHODS: A randomized, double-blind, controlled trial with 110 children was conducted. The subjects were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements (SBMs) ≥ 3 per week were the main outcomes and the risk ratio (RR) with 95% CI was calculated. Changes in the intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms. RESULTS: At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 SBMs per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; RR: 1.364, 95% CI: 1.063-1.749; P<0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms. CONCLUSIONS: FMT enhances the efficacy of RCE and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.
ABSTRACT
This study aimed to develop a deep learning model to predict the risk stratification of all-cause death for older people with disability, providing guidance for long-term care plans. Based on the government-led long-term care insurance program in a pilot city of China from 2017 and followed up to 2021, the study included 42,353 disabled adults aged over 65, with 25,071 assigned to the training set and 17,282 to the validation set. The administrative data (including baseline characteristics, underlying medical conditions, and all-cause mortality) were collected to develop a deep learning model by least absolute shrinkage and selection operator. After a median follow-up time of 14 months, 17,565 (41.5%) deaths were recorded. Thirty predictors were identified and included in the final models for disability-related deaths. Physical disability (mobility, incontinence, feeding), adverse events (pressure ulcers and falls from bed), and cancer were related to poor prognosis. A total of 10,127, 25,140 and 7086 individuals were classified into low-, medium-, and high-risk groups, with actual risk probabilities of death of 9.5%, 45.8%, and 85.5%, respectively. This deep learning model could facilitate the prevention of risk factors and provide guidance for long-term care model planning based on risk stratification.
Subject(s)
Deep Learning , Long-Term Care , Humans , Female , Male , Aged , China/epidemiology , Prospective Studies , Aged, 80 and over , Cause of Death , Disabled Persons/statistics & numerical data , Risk Assessment , Mortality/trends , Risk Factors , PrognosisABSTRACT
Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.
ABSTRACT
BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.
Subject(s)
Aristolochic Acids , Kidney Diseases , Transcription Factors , Aristolochic Acids/toxicity , Transcription Factors/genetics , Transcription Factors/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/genetics , Animals , Mice , Humans , Activating Transcription Factor 3/genetics , Activating Transcription Factor 3/metabolism , Protein Interaction MapsABSTRACT
The mitochondrial enzyme arginase-2 (Arg-2) is implicated in the pathophysiology of contrast-induced acute kidney injury (CI-AKI). Therefore, Arg-2 represents a candid target for CI-AKI prevention. Here, layer-by-layer (LbL) assembled renal-targeting polymeric nanoparticles are developed to efficiently deliver small interfering RNA (siRNA), knockdown Arg-2 expression in renal tubules, and prevention of CI-AKI is evaluated. First, near-infrared dye-loaded poly(lactic-co-glycolic acid) (PLGA) anionic cores are electrostatically coated with cationic chitosan (CS) to facilitate the adsorption and stabilization of Arg-2 siRNA. Next, nanoparticles are coated with anionic hyaluronan (HA) to provide protection against siRNA leakage and shielding against early clearance. Sequential electrostatic layering of CS and HA improves loading capacity of Arg-2 siRNA and yields LbL-assembled nanoparticles. Renal targeting and accumulation is enhanced by modifying the outermost layer of HA with a kidney targeting peptide (HA-KTP). The resultant kidney-targeting and siRNA loaded nanoparticles (PLGA/CS/HA-KTP siRNA) exhibit proprietary accumulation in kidneys and proximal tubular cells at 24 h post-tail vein injection. In iohexol-induced in vitro and in vivo CI-AKI models, PLGA/CS/HA-KTP siRNA delivery alleviates oxidative and nitrification stress, and rescues mitochondrial dysfunction while reducing apoptosis, thereby demonstrating a robust and satisfactory therapeutic effect. Thus, PLGA/CS/HA-KTP siRNA nanoparticles offer a promising candidate therapy to protect against CI-AKI.
Subject(s)
Acute Kidney Injury , Arginase , Contrast Media , Nanoparticles , Polylactic Acid-Polyglycolic Acid Copolymer , RNA, Small Interfering , Nanoparticles/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism , Animals , RNA, Small Interfering/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Contrast Media/chemistry , Mice , Arginase/metabolism , Arginase/genetics , Chitosan/chemistry , Gene Knockdown Techniques , Kidney/metabolism , Kidney/drug effects , Kidney/pathology , Hyaluronic Acid/chemistry , Male , Humans , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Layer-by-Layer NanoparticlesABSTRACT
Staphylococcus aureus, the principal causative agent of osteomyelitis, can be internalized by osteoblasts and thereby escape from immune phagocytes and many kinds of antibiotics. To deliver antibiotics into osteoblasts to kill S. aureus in the intracellular environment, we developed gentamicin-loaded chitosan nanoparticles and evaluated their intracellular bactericidal effect. We found decreased numbers of S. aureus cells in infected osteoblasts treated with gentamicin-loaded chitosan nanoparticles. The cytotoxicity of the nanoparticles was evaluated by CCK-8 assay. There was no significant viability decrease at all tested concentrations. In conclusion, our results provide evidence for the potential use of gentamicin-loaded chitosan nanoparticles to enhance the delivery of gentamicin into cells and for their antibacterial effect against internalized S. aureus in the intracellular environment of osteoblasts.
Subject(s)
Anti-Bacterial Agents , Chitosan , Gentamicins , Nanoparticles , Osteoblasts , Staphylococcus aureus , Gentamicins/pharmacology , Chitosan/pharmacology , Chitosan/chemistry , Staphylococcus aureus/drug effects , Osteoblasts/drug effects , Anti-Bacterial Agents/pharmacology , Nanoparticles/chemistry , Animals , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Humans , Cell Survival/drug effects , MiceABSTRACT
Originating in the early 20th century, ultrasonic testing has found increasingly extensive applications in medicine, industry, and materials science. Achieving both a high signal-to-noise ratio and high efficiency is crucial in ultrasonic testing. The former means an increase in imaging clarity as well as the detection depth, while the latter facilitates a faster refresh of the image. It is difficult to balance these two indicators with a conventional short pulse to excite the probe, so in general handling methods, these two factors have a trade-off. To solve the above problems, coded excitation (CE) can increase the pulse duration and offers great potential to improve the signal-to-noise ratio with equivalent or even higher efficiency. In this paper, we first review the fundamentals of CE, including signal modulation, signal transmission, signal reception, pulse compression, and optimization methods. Then, we introduce the application of CE in different areas of ultrasonic testing, with a focus on industrial bulk wave single-probe detection, industrial guided wave detection, industrial bulk wave phased array detection, and medical phased array imaging. Finally, we point out the advantages as well as a few future directions of CE.
ABSTRACT
BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.
Subject(s)
Acute Lung Injury , Gastrointestinal Microbiome , Lipopolysaccharides , STAT3 Transcription Factor , T-Lymphocytes, Regulatory , Th17 Cells , Animals , Acute Lung Injury/drug therapy , T-Lymphocytes, Regulatory/drug effects , Gastrointestinal Microbiome/drug effects , Th17 Cells/drug effects , Male , Mice , STAT3 Transcription Factor/metabolism , Disease Models, Animal , Mice, Inbred BALB C , Mice, Inbred C57BL , Anti-Inflammatory Agents/pharmacology , Bronchoalveolar Lavage Fluid/cytologyABSTRACT
Power transmission is an important application for magnetorheological (MR) fluid, and the cylinder-type power transmission device is a novel transmission form due to its high stability, higher transmission torque, and large ratio of power to mass. This work designed a novel multi-cylinder transmission device with a water-cooling channel because the MR transmission device, especially high-power MR transmission device, inevitably works in the high-temperature environment. Based on Ohm's law and electromagnetism theory, the magnetic circuit in the novel MR transmission device is designed, and the magnetoresistance was calculated. The finite element method is used to analyze the magnetic field in the device to ensure that the magnetic field in the working gap of MR fluid is strong enough for the MR effects. The temperature of the MR fluid inside the device is analyzed by the finite element method in the natural cooling state and the water-cooling state, respectively, so as to obtain the performance of water cooling. The novel MR transmission device is manufactured to verify its power transmission capability and heat-dissipation performance. The experimental results show that the novel device can transmit a maximum torque of 70 N m, consistent with the rated torque. In addition, compared with natural cooling, the water cooling makes the temperature of the MR fluid to drop by 32.7% under the same working condition. This is the first time that the cooling channel is set up in the cylinder-type MR transmission device, which will provide a solution for the higher power transmission capacity by MR fluid.
ABSTRACT
PURPOSE: Vitamin D receptors (VDR) play important roles in cardiovascular, immune, metabolic and other functions. Activation of VDR may help improve endothelial dysfunction, atherosclerosis, vascular calcification, and cardiac hypertrophy. However, the specific target genes and mechanisms of VDR in improving Human Umbilical Vein Endothelial Cell (HUVEC) functions remain unclear. This study aims to investigate the function and mechanism of VDR in HUVECs. METHODS: Endothelial dysfunction cell model was constructed by oxidized low-density lipoprotein (ox-LDL). An animal model of atherosclerosis was established in male homozygous Apoe-/- mice (6 weeks) on a high fat diet for 6 weeks. The relationship between VDR and adrenomedullin (ADM) was studied by bioinformatics analysis, ChIP, and luciferase reporter gene analysis. Endothelial cell function was evaluated by Transwell migration and Tube Formation tests. Ferroptosis was detected by measuring intracellular iron content, levels of oxidative stress markers, and ferroptosis related proteins. RESULTS: Overexpression of VDR in HUVECs inhibits ox-LDL-induced endothelial dysfunction and ferroptosis. VDR binds to the ADM promoter sequence and regulates the transcription of ADM. Inhibition of ADM promotes ox-LDL-induced endothelial dysfunction and ferroptosis. ADM regulates ox-LDL-induced endothelial dysfunction and ferroptosis through the AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice inhibited lipid deposition and plaque area in atherosclerotic mice. CONCLUSION: VDR inhibits ox-LDL-induced endothelial dysfunction and ferroptosis by regulating ADM transcription and acting on AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice reduced lipid deposition and plaque area in the thoracic aorta of atherosclerotic mice.
Subject(s)
Adrenomedullin , Atherosclerosis , Endothelial Cells , Ferroptosis , Receptors, Calcitriol , Signal Transduction , Humans , Animals , Mice , Mice, Inbred C57BL , Random Allocation , Atherosclerosis/metabolism , Atherosclerosis/pathology , Receptors, Calcitriol/metabolism , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Human Umbilical Vein Endothelial Cells , Lipoproteins, LDL/metabolism , AMP-Activated Protein Kinases/metabolism , Male , Adrenomedullin/genetics , Adrenomedullin/metabolism , Diet, High-FatABSTRACT
Deltamethrin, an important pyrethroid insecticide, is frequently detected in human samples. This study aims to assess the potential effects of deltamethrin on human health and investigate the patterns of residue enrichment and elimination in 112 healthy laying hens. These hens were administered 20 mg·kg-1 deltamethrin based on their body weight. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the residue enrichment pattern and elimination pattern of deltamethrin in the hens. The results indicated a significant increase in the concentration of deltamethrin in chicken manure during the treatment period. By the 14th day of administration, the concentration of deltamethrin in the stool reached 13,510.9 ± 172.24 µg·kg-1, with a fecal excretion rate of 67.56%. The pulmonary deltamethrin concentration was the second highest at 3844.98 ± 297.14 µg·kg-1. These findings suggest that chicken feces contain substantial amounts of deltamethrin after 14 days of continuous administration, and that it can easily transfer to the lungs. After 21 days of drug withdrawal, the residual concentration of deltamethrin in the fat of laying hens was 904.25 ± 295.32 µg·kg-1, with a half-life of 17 days and a slow elimination rate. In contrast, the lungs showed relatively low elimination half-lives of 0.2083 days, indicating faster elimination of deltamethrin in this tissue. These results highlight differences in the rate of deltamethrin elimination in different tissues during drug withdrawal. The fat of laying hens exhibited the highest residue of deltamethrin and the slowest elimination rate, while the lungs showed the fastest elimination rate. Moreover, deltamethrin was found to accumulate in the edible tissues of eggs and laying hens, suggesting that humans may be exposed to deltamethrin through food.
ABSTRACT
Nonclassical quantum states are the pivotal features of a quantum system that differs from its classical counterpart. However, the generation and coherent control of quantum states in a macroscopic spin system remain an outstanding challenge. Here we experimentally demonstrate the quantum control of a single magnon in a macroscopic spin system (i.e., 1 mm-diameter yttrium-iron-garnet sphere) coupled to a superconducting qubit via a microwave cavity. By tuning the qubit frequency in situ via the Autler-Townes effect, we manipulate this single magnon to generate its nonclassical quantum states, including the single-magnon state and the superposition of single-magnon state and vacuum (zero magnon) state. Moreover, we confirm the deterministic generation of these nonclassical states by Wigner tomography. Our experiment offers the first reported deterministic generation of the nonclassical quantum states in a macroscopic spin system and paves a way to explore its promising applications in quantum engineering.
ABSTRACT
The NAC (NAM, ATAF1/2, and CUC2) transcription factors (TF), one of the largest plant-specific gene families, play important roles in the regulation of plant growth and development, stress response and disease resistance. In particular, several NAC TFs have been identified as master regulators of secondary cell wall (SCW) biosynthesis. Iron walnut (Juglans sigillata Dode), an economically important nut and oilseed tree, has been widely planted in the southwest China. The thick and high lignified shell derived endocarp tissues, however, brings troubles in processing processes of products in industry. It is indispensable to dissect the molecular mechanism of thick endocarp formation for further genetic improvement of iron walnut. In the present study, based on genome reference of iron walnut, 117 NAC genes, in total, were identified and characterized in silico, which involves only computational analysis to provide insight into gene function and regulation. We found that the amino acids encoded by these NAC genes varied from 103 to 1,264 in length, and conserved motif numbers ranged from 2 to 10. The JsiNAC genes were unevenly distributed across the genome of 16 chromosomes, and 96 of these genes were identified as segmental duplication genes. Furthermore, 117 JsiNAC genes were divided into 14 subfamilies (A-N) according to the phylogenetic tree based on NAC family members of Arabidopsis thaliana and common walnut (Juglans regia). Furthermore, tissue-specific expression pattern analysis demonstrated that a majority of NAC genes were constitutively expressed in five different tissues (bud, root, fruit, endocarp, and stem xylem), while a total of 19 genes were specifically expressed in endocarp, and most of them also showed high and specific expression levels in the middle and late stages during iron walnut endocarp development. Our result provided a new insight into the gene structure and function of JsiNACs in iron walnut, and identified key candidate JsiNAC genes involved in endocarp development, probably providing mechanistic insight into shell thickness formation across nut species.
ABSTRACT
OBJECTIVE: The study was conducted to assess the effect of supplementation with Lactobacillus lactis (LL) on growth performance, hematological parameters, meat quality and intestinal flora in pigs from growing until slaughter. METHODS: A total of 72 growing pigs (30.46 ± 3.08 kg) were randomly assigned to 3 groups (including 3 pens for each group, with 8 pigs in each pen). The three treatments comprised a basal diet (O-0) and two experimental diets supplemented for 14 weeks with 0.01% (O-100) and 0.03% (O-300) LL, respectively. RESULTS: The final body weights of the pigs in the O-100 and O-300 groups were significantly higher (p < 0.05) than those of the O-0 group. In the grower phase, the average daily weight gain (ADG) and average daily feed intake (ADFI) of pigs fed the O-300 diet were higher (p < 0.05) than those of pigs fed the O-0 diet during the grower phase. BUN and MDA were significantly higher (p < 0.05 for all) in the O-0 group than in the O-100 and O-300 groups during the grower phase. No difference (p > 0.05) was observed in the hematological parameters among the three groups during the finisher phase. Counts of LL in the stomach were significantly higher (p < 0.05) in the O-300 group than in the O-0 group. Counts of Escherichia coli in the jejunum were significantly higher (p < 0.05) in the O-0 group than in the O-300 group. Furthermore, the hardness, cohesiveness, gumminess and resilience of longissimus dorsi muscle collected from pigs fed the O-300 diet were higher (p < 0.01; p = 0.024; p = 0.003; p = 0.014, respectively) than those of tissue collected from pigs fed the O-0 diet. CONCLUSION: Dietary LL supplementation increased final body weight, increased ADG in the grower phase and enhanced meat quality.
ABSTRACT
Background: Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers. Methods: Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples. Results: 95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro. External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI. Conclusion: The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.
Subject(s)
Acute Kidney Injury , Toll-Like Receptor 4 , Animals , Mice , Toll-Like Receptor 4/genetics , Transcriptome , Vancomycin/adverse effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/geneticsABSTRACT
Cancer immunotherapies, including immune checkpoint inhibition (ICI) and adoptive immune cells therapy, are promising therapeutic strategies. They reactivate the function of immune cells and induce immune responses to attack tumor cells. Although these novel therapies benefited a large amount of cancer patients, many cancer patients have shown fair responses even resistance to cancer immunotherapies, limiting their wide clinical application. Therefore, it is urgent to explore the underlying mechanisms of low response and resistance of cancer immunotherapy to enhance their treatment efficacy. The programmed cell death (PCD) including the ferroptosis, has been demonstrated to play essential roles in antitumor immunity and in regulating the immune response to ICIs. Ferroptosis, a phospholipid peroxidation-mediated, iron-dependent membrane damage, exhibite three critical hallmarks: the oxidation of phospholipids, the lack of lipid peroxide repair capability and the overloading of redox-active iron. Notably, ferroptosis was found to plays important roles in regulating tumor immunity and response to immunotherapy. Therefore, targeting ferroptosis alone or in combination with immunotherapy may provide novel options to promote their antitumor efficacy. However, the effect of ferroptosis on tumor immunity and immunotherapy is affected by the interaction of ferroptosis and cancer cells, immune cells, tumor microenvironment (TME) and others. In this review, we summarized and discussed the critical roles of ferroptosis in regulating antitumor immunity, TME and in the improvement of the therapeutic efficacy of immunotherapy in cancers.
Subject(s)
Ferroptosis , Humans , Immunotherapy , Apoptosis , Cell- and Tissue-Based Therapy , Iron , PhospholipidsABSTRACT
Chemical synthesis is state-of-the-art, and, therefore, it is generally based on chemical intuition or experience of researchers. The upgraded paradigm that incorporates automation technology and machine learning (ML) algorithms has recently been merged into almost every subdiscipline of chemical science, from material discovery to catalyst/reaction design to synthetic route planning, which often takes the form of unmanned systems. The ML algorithms and their application scenarios in unmanned systems for chemical synthesis were presented. The prospects for strengthening the connection between reaction pathway exploration and the existing automatic reaction platform and solutions for improving autonomation through information extraction, robots, computer vision, and intelligent scheduling were proposed.
ABSTRACT
Exosomes are a subtype of extracellular vesicles (EVs) with a size range between 30 and 150 ânm, which can be released by the majority of cell types and circulate in body fluid. They function as a long-distance cell-to-cell communication mechanism that modulates the gene expression profile and fate of target cells. Increasing evidence has indicated exosomes' central role in regulating various complex reproductive processes. However, to our knowledge, a review that focally and vividly describes the role of exosomes in reproductive development is still lacking. This review highlights our knowledge about the contribution of exosomes to early mammalian reproduction, such as gametogenesis, fertilization, early embryonic development, implantation, placentation and pregnancy. The discussion is primarily drawn from literature pertaining to the mammalian lineage with emphasis on the roles of exosomes in human reproduction and laboratory and livestock models.
ABSTRACT
An optical blackbody is an ideal absorber for all incident optical radiation, and the theoretical study of its radiation spectra paved the way for quantum mechanics (Planck's law). Herein, we propose the concept of an electron blackbody, which is a perfect electron absorber as well as an electron emitter with standard energy spectra at different temperatures. Vertically aligned carbon nanotube arrays are electron blackbodies with an electron absorption coefficient of 0.95 for incident energy ranging from 1 keV to 20 keV and standard electron emission spectra that fit well with the free electron gas model. Such a concept might also be generalized to blackbodies for extreme ultraviolet, X-ray, and γ-ray photons as well as neutrons, protons, and other elementary particles.