ABSTRACT
Establishing an intimate relationship between similar individuals is the beginning of self-extension. Various self-similar chiral nanomaterials can be designed using an individual-to-family approach, accomplishing self-extension. This self-similarity facilitates chiral communication, transmission, and amplification of synthons. We focus on describing the marriage of discrete cages to develop self-similar extended frameworks. The advantages of utilizing cage-based frameworks for chiral recognition, enantioseparation, chiral catalysis and sensing are highlighted. To further promote self-extension, fractal chiral nanomaterials with self-similar and iterated architectures have attracted tremendous attention. The beauty of a fractal family tree lies in its ability to capture the complexity and interconnectedness of a family's lineage. As a type of fractal material, nanoflowers possess an overarching importance in chiral amplification due to their large surface-to-volume ratio. This review summarizes the design and application of state-of-the-art self-similar chiral nanomaterials including cage-based extended frameworks, fractal nanomaterials, and nanoflowers. We hope this formation process from individuals to families will inherit and broaden this great chirality.
ABSTRACT
Competition is common in life, and intimate relationships are essential. Understanding how intimate relationships impact an individual's competitive process is crucial. This study explored the impact of competitor gender on female competition using electroencephalography analysis. The results revealed that females exhibited a smaller median of the absolute value of reaction time difference (DRT) between their partners and their competitors when their partners were absent compared to when their partners were present. Additionally, females showed greater average amplitudes of N2 posterior contralateral component (N2pc) and Late Positive Potential (LPP), increased activation of the alpha frequency band, and enhanced theta frequency band functional connectivity between the central parietal lobe and occipital lobe. Furthermore, when competing with individuals of the same gender as opposed to individuals of the opposite gender, females exhibited greater average amplitudes of percentage of wins and N2pc. A significant negative correlation was noted between the DRT and the average wave amplitudes of N2pc and LPP. These findings suggest that females are more engaged in competitive tasks when partners are not present and have improved decision-making when competing with same-gender individuals. This study provides evidence for the influence of lovers on female competition, helping females adapt to social competition and promoting healthy relationships.
Subject(s)
Brain , Competitive Behavior , Electroencephalography , Interpersonal Relations , Humans , Female , Young Adult , Brain/physiology , Adult , Competitive Behavior/physiology , Reaction Time/physiology , Evoked Potentials/physiology , MaleABSTRACT
Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.
Subject(s)
Genome , Nuclear Transfer Techniques , Animals , Swine , Gene Expression Regulation, Developmental , Homeodomain Proteins/metabolism , Homeodomain Proteins/genetics , Embryonic Development/genetics , Embryo, Mammalian/metabolism , Humans , Transcription Factors/metabolism , Transcription Factors/genetics , Acetylation , Cloning, Organism/methods , Histones/metabolism , Blastocyst/metabolismABSTRACT
Natronorubrum daqingense JX313T is an extremely halophilic archaea that can grow in a NaCl-saturated environment. The excellent salt tolerance of N. daqingense makes it a high-potential candidate for researching the salt stress mechanisms of halophilic microorganisms from Natronorubrum. In this study, transcriptome analysis revealed that three genes related to the biosynthesis of vitamin B12 were upregulated in response to salt stress. For the wild-type (WT) strain JX313T, the low-salt adaptive mutant LND5, and the vitamin B12 synthesis-deficient strain ΔcobC, the exogenous addition of 10 mg/L of vitamin B12 could maximize their cell survival and biomass in both optimal and salt stress environments. Knockout of cobC resulted in changes in the growth boundary of the strain, as well as a significant decrease in cell survival and biomass, and the inability to synthesize vitamin B12. According to the HPLC analysis, when the external NaCl concentration (w/v) increased from 17.5% (optimal) to 22.5% (5% salt stress), the intracellular accumulation of vitamin B12 in WT increased significantly from (11.54 ± 0.44) mg/L to (15.23 ± 0.20) mg/L. In summary, N. daqingense is capable of absorbing or synthesizing vitamin B12 in response to salt stress, suggesting that vitamin B12 serves as a specific compatible solute effector for N. daqingense during salt stress.
Subject(s)
Gene Expression Profiling , Salt Stress , Vitamin B 12 , Vitamin B 12/metabolism , Sodium Chloride/pharmacology , Transcriptome , Salt Tolerance/genetics , Gene Expression Regulation, ArchaealABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Sanmiao wan (SMW), a classical traditional Chinese medicine (TCM) formula, has been employed to treat gouty diseases in clinic as early as Yuan dynasty. It shows remarkably therapeutic effects in acute gouty arthritis (GA). However, the potential mechanisms of SMW are still not fully revealed. AIM OF THE STUDY: The objective of this project is to evaluate the pharmacological effects and possible mechanisms of SMW in a rat model of acute GA. MATERIALS AND METHODS: Monosodium urate (MSU) suspension was injected into the ankle joint of rats to establish acute GA model. The inflammation was evaluated by measuring the posterior ankle diameter. The pathological status of synovial tissue was assessed by hematoxylin eosin (HE), Masson, and picrosirius red staining. The level of IL-6 was measured using ELISA kit. The levels of blood urea nitrogen (BUN), creatinine (CR), UA (uric acid), and xanthine oxidase (XOD) in the serum were measured using standard diagnostic kits. The percentage of Th17 cells in blood samples was performed using flow cytometry. Moreover, RT-qPCR was performed to examine the mRNA level of RANK, RORγt, RANKL, and STAT3 in the synovial tissue. Furthermore, immunofluorescence was carried out to assess the expression of STAT3 in the synovial tissue. RESULTS: SMW effectively alleviated the inflammation and improved the pathological status of the ankle joint in rats with acute GA. It significantly suppressed the release of proinflammatory cytokine (IL-6). Meanwhile, the levels of UA, BUN, and CR were markedly reduced after SMW treatment. A remarkable reduction of XOD activity was observed in the study. Importantly, SMW treatment significantly reduced the frequency of Th17 cells, decreased the mRNA levels of RANK, RORγt, RANKL, and STAT3 in the synovial tissue. Furthermore, the suppression of STAT3 was also demonstrated using immunofluorescence in SMW-treated group. CONCLUSION: SMW showed significant anti-inflammatory and hypouricemic effects in a rat model of GA. It is an effective TCM formula for GA therapy.
Subject(s)
Arthritis, Gouty , Rats , Animals , Arthritis, Gouty/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3 , Interleukin-6 , Inflammation/drug therapy , Uric Acid , RNA, MessengerABSTRACT
The discovery of the role of autophagy, particularly the selective form like ferritinophagy, in promoting cells to undergo ferroptosis has inspired us to investigate functional connections between diseases and cell death. Ferroptosis is a novel model of procedural cell death characterized by the accumulation of iron-dependent reactive oxygen species (ROS), mitochondrial dysfunction, and neuroinflammatory response. Based on ferroptosis, the study of ferritinophagy is particularly important. In recent years, extensive research has elucidated the role of ferroptosis and ferritinophagy in neurological diseases and anemia, suggesting their potential as therapeutic targets. Besides, the global emergence and rapid transmission of COVID-19, which is caused by SARS-CoV-2, represents a considerable risk to public health worldwide. The potential involvement of ferroptosis in the pathophysiology of brain injury associated with COVID-19 is still unclear. This review summarizes the pathophysiological changes of ferroptosis and ferritinophagy in neurological diseases, anemia, and COVID-19, and hypothesizes that ferritinophagy may be a potential mechanism of ferroptosis. Advancements in these fields will enhance our comprehension of methods to prevent and address neurological disorders, anemia, and COVID-19.
Subject(s)
Anemia , Brain Injuries , COVID-19 , Ferroptosis , Humans , AutophagyABSTRACT
Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos. Current studies have illustrated several pioneer factors as being important for agricultural animals, but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear. By employing low-input DNase-seq (liDNase-seq), we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development. Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos. Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos, whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts. Furthermore, KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos. In addition, we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation, whereas knockdown of KLF4 disrupted this process. Taken together, our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.
Subject(s)
Chromatin , Embryonic Development , Swine , Animals , Embryonic Development/genetics , Chromatin/genetics , Chromatin/metabolism , Blastocyst/metabolism , ChromosomesABSTRACT
BACKGROUND: In China, Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall (Biazhu-Baishao, BZBS) is a classic herb pair used to treat intestinal stress syndrome, ulcerative colitis and other diseases. However, the mechanism of BZBS in the treatment of functional constipation (FC) has been little studied and remains unclear. In this study, a behavioral investigation, colon tissue morphology, enzyme-linked immunosorbent assay (Elisa) and intestinal microflora analysis have been used to illuminate the potential mechanism of the effects of BZBS on FC in a rat model. METHODS: A FC rat model was constructed and BZBS was given as treatment. Observations and recordings were made of the fecal moisture content, the defecation time of the first black stool, and the rate of intestinal propulsion. Elisa was used to detect the expression levels of substance P (SP), vasoactive intestinal peptide (VIP), 5-hydroxytryptamine (5-HT) in the colon. To ascertain the composition of the microbial community, a high throughput 16S ribosomal RNA (16S rRNA) gene sequencing technique was employed. RESULTS: Oral administration of BZBS significantly ameliorated several key excretion parameters, including the time to first black stool defecation, stool water content, and the propulsion rate in the small intestine in FC rats. It increased the expression of SP, VIP and 5-HT in the colon. 16S rRNA gene sequencing results showed that BZBS changed the microbial community structure, decreased the Bacteroidetes/Firmicutes ratio, increased the relative abundance of Blautia and Fusicatenibacter, and decreased the relative abundance of Ruminococcus and Roseburia. CONCLUSIONS: BZBS effectively alleviates FC and improves dysbacteriosis.
Subject(s)
Gastrointestinal Microbiome , Rats , Animals , RNA, Ribosomal, 16S/genetics , Serotonin , Constipation/drug therapy , Constipation/genetics , Vasoactive Intestinal Peptide/pharmacology , Vasoactive Intestinal Peptide/genetics , Substance PABSTRACT
We have successfully identified the transcription factor Cmr1 from the fungus Aureobasidium pullulans Hit-lcy3T, which regulates melanin biosynthesis genes. Bioinformatics analysis revealed that the Cmr1 gene encodes a protein of 945 amino acids, containing two Cys2His2 zinc finger domains and a Zn(II)2Cys6 binuclear cluster domain located at the N-terminus of Cmr1. To investigate the function of the Cmr1 gene, we performed gene knockout and overexpression experiments. Our results showed that Cmr1 is a key regulator of melanin synthesis in Hit-lcy3T, and its absence caused developmental defects. Conversely, overexpression of Cmr1 significantly increased the number of chlamydospores in Hit-lcy3T and improved melanin production. RT-qPCR analysis further revealed that overexpression of Cmr1 enhanced the expression of several genes involved in melanin biosynthesis, including Cmr1, PKS, SCD1, and THR1. Melanin extracted from the Hit-lcy3T was characterized using UV and IR spectroscopy. Furthermore, we assessed the antioxidant properties of Hit-lcy3T melanin and found that it possesses strong scavenging activity against DPPH·, ABTS·, and OH·, but weaker activity against O2-·. These findings suggest that Hit-lcy3T melanin holds promise for future development as a functional food additive.
ABSTRACT
The ability of the fungus to regulate metabolism on various nitrogen sources makes it survive and metabolize in different environments. The biomass and the ß-glucan yield of Aureobasidium pullulans are closely associated with the nitrogen source. This study found the only GATA nitrogen source activation regulating factor Area in HIT-LCY3. In order to testify the Area function, we amplified its conserved domain to build a silencing vector and used the RNAi to obtain the Area silent strain, and then explored its effect on the phenotype of A. pullulans and the yield of ß-glucan. We found that the biomass and ß-glucan yield of the silent strain decreased significantly after culturing with different nitrogen sources, in particular when using sodium nitrate and glutamate as the source. However, the ß-glucan yield increased significantly after overexpression of Area, reaching 5.2 g/L when glutamine was the nitrogen source. In addition, the strain morphology changed as well under different nitrogen sources. At last, we investigated the antioxidant activity in vitro of ß-glucan and found that it has a significant clearance effect on OH·, DPPH·, and ABTS·, being best with ABTS. Therefore, this study believed that the Area gene has a certain regulation function on the synthesis of ß-glucan with antioxidant activity.
ABSTRACT
Brain-inspired neuromorphic computing hardware based on artificial synapses offers efficient solutions to perform computational tasks. However, the nonlinearity and asymmetry of synaptic weight updates in reported artificial synapses have impeded achieving high accuracy in neural networks. Here, this work develops a synaptic memtransistor based on polarization switching in a two-dimensional (2D) ferroelectric semiconductor (FES) of α-In2 Se3 for neuromorphic computing. The α-In2 Se3 memtransistor exhibits outstanding synaptic characteristics, including near-ideal linearity and symmetry and a large number of programmable conductance states, by taking the advantages of both memtransistor configuration and electrically configurable polarization states in the FES channel. As a result, the α-In2 Se3 memtransistor-type synapse reaches high accuracy of 97.76% for digit patterns recognition task in simulated artificial neural networks. This work opens new opportunities for using multiterminal FES memtransistors in advanced neuromorphic electronics.
Subject(s)
Electronics , Semiconductors , Neural Networks, Computer , SynapsesABSTRACT
BACKGROUND: We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz. (AMK) and Paeonia lactiflora Pall. (PLP). METHODS: The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. A database of functional constipation targets was established by GeneCard and OMIM. An "ingredient-target" network map was constructed with Cytoscape software (version 3.7.1), and molecular docking analysis was performed on the components and genes with the highest scores. The rats in the normal group were given saline, and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days. The serum and intestinal tissue levels of adenosine monophosphate (cAMP), protein kinase A (PKA), and adenylyl cyclase (AC) of the rats and aquaporin (AQP)1, AQP3, and AQP8 were measured. RESULTS: AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. After treatment with AMK, PLP, or mosapride, the serum and intestinal tissue levels of AC, cAMP, and PKA were significantly downregulated. Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1, AQP3, and AQP8 to varying degrees. CONCLUSION: Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. Studies have confirmed that AMK and PLP can also affect AC, cAMP, and PKA. AC, cAMP, and PKA in model rats were significantly downregulated. AQP expression is closely related to AC, cAMP, and PKA. AMK and PLP can reduce the expression of AQP1, AQP3, and AQP9 in the colon of constipated rats.
Subject(s)
Aquaporins , Atractylodes , Paeonia , Animals , Constipation/drug therapy , Cyclic AMP-Dependent Protein Kinases/therapeutic use , Medicine, Chinese Traditional , Molecular Docking Simulation , RatsABSTRACT
The mutant p53 plays a vital role in the control of cell survival and division under various stresses, including apoptosis and ferroptosis. Here, we showed that eupaformosanin (Eup), a natural compound isolated from Eupatorium cannabinum Linn., significantly inhibited the viability of triple-negative breast cancer (TNBC) cells. Meanwhile, mitochondrial apoptosis contributed to the apoptosis induced by Eup, followed by the disruption of mitochondrial membrane potential (MMP; Δψm) and accumulation of mitochondrial ROS (mt ROS). Apoptosis inhibitor Z-VAD rescued Eup-induced cell death. Afterward, ferroptosis-induced cell death was demonstrated after treatment with Eup, accompanied by lipid reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and iron increase. These events were blocked by ferroptosis inhibitors ferrostatin-1 (Fer-1), deferoxamine (DFO), and liproxstatin-1 (lip-1), indicating that ferroptosis facilitated Eup-induced cell death. Furthermore, Eup regulated mutant p53 ubiquitination. Mutant p53 signaling pathway participated in Eup-induced apoptosis and ferroptosis, which were rescued when mutant p53 was silent in TNBC cells. Also, Eup exerted an anti-TNBC effect by inducing apoptosis and ferroptosis in vivo. Taken together, the data demonstrate that the natural compound Eup is a potential TNBC therapeutic agent that induces apoptosis and ferroptosis through ubiquitination of mutant p53.
Subject(s)
Ferroptosis , Triple Negative Breast Neoplasms , Apoptosis , Cell Line, Tumor , Glutathione/metabolism , Humans , Reactive Oxygen Species/metabolism , Terpenes , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , UbiquitinationABSTRACT
Increasing evidence has indicated that oxidative stress is associated with the health of infants. Bifidobacterium, especially B. longum subsp. longum strains, are abundant in the gut microbiota of infants, which may have the potential to ameliorate oxidative damage. Thus, this study aimed to isolate and screen B. longum subsp. longum strains with probiotic characters and antioxidant properties as infants' dietary supplements. In this study, 24 B. longum subsp. longum strains were isolated from 15 healthy infants identified via 16S rRNA and heat shock protein 60 (hsp60) sequences. B. longum subsp. longum B13, F2, K4, K5, K10, K13, and K15 strains were selected based on high values obtained from autoaggregation, hydrophobicity, and adhesion assays to HT-29 cells. Among these seven strains, B. longum subsp. longum F2, K5, K10, and K15 were selected according to the high tolerance of gastrointestinal tract conditions compared to Bifidobacterium animalis subsp. lactis BB-12. Among these four strains, B. longum subsp. longum K5 was susceptible to common antibiotics and showed the highest intestinal epithelial cell proliferation of CCD 841 CoN. Additionally, B. longum subsp. longum K5 showed a strong antioxidant capacity, and its supernatant exhibited better activity of reducing power, hydroxyl radical scavenging, and DPPH radical scavenging than that of the intact cells with cell-free extracts. The findings indicated that B. longum subsp. longum K5 could be used as a probiotic candidate in infant nutrition.
ABSTRACT
BACKGROUND: Viral pneumonia (VP) is a common inflammatory disease caused by a virus in the upper respiratory tract. However, current treatment options for pneumonia are limited because of the strong infectivity and lack of research. METHOD: Based on various databases, the mechanisms of Ginger and Forsythia were predicted by network pharmacology. The possible active ingredients of Ginger and Forsythia were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened by pharmacokinetic parameters. Their possible targets were predicted by the TCMSP database. The VP-related targets were collected from the GeneCards and OMIM databases. The compound-target-disease network was visualized by Cytoscape 3.7.1. In addition, the protein functional annotation and identification of signalling pathways of possible targets were performed with Gene Ontology (GO) and KEGG enrichment analysis. Molecular docking was finally employed for in silico simulation matching between representative Ginger and Forsythia compounds and their core genes. RESULTS: Twenty-eight active ingredients of Ginger and Forsythia were found and 30 common targets for the combined treatment of VP were obtained. The enrichment analysis of GO functions and KEGG pathways included 186 GO function entries and 56 KEGG pathways. Molecular docking showed that the main ingredients can closely bind three targets (CASP3, JUN, and ESR1). Thus, Ginger and Forsythia play significant roles in the prevention and treatment of VP, and this study showed their mechanism was "multicomponent, multitarget, and multipathway" for the prevention and treatment of VP. CONCLUSION: We successfully predicted the active components and targets of Ginger and Forsythia for prevention and treatment of VP. This may systematically clarify its mechanism of action and provide a direction for future research.