Analysis of mechanism of core points in acupuncture and moxibustion treatment for epilepsy based on data mining. / åŸºäºŽæ•°æ®æŒ–æŽ˜æŽ¢è®¨é’ˆç¸æ²»ç–—ç™«ç—«æ ¸å¿ƒç©´ä½çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To explore the mechanism of core points in acupuncture and moxibustion treatment for epilepsy by using data mining technique, so as to provide a reference for clinical practice and experimental research. METHODS: The data comes from relevant documents collected from CNKI, Wanfang, SinoMed, VIP, PubMed, Embase, Cochrane Library, EBSCO, Web of Science databases. The selected acupoints were analyzed in descriptive statistics, high-frequency acupoints group and core acupoint prescription. Further, potential target mining, "core acupoint prescription-target-epilepsy" network construction, protein-protein interactions (PPI) network establishment and core target extraction, gene ontology (GO) and KEGG gene enrichment analysis of the core acupoint prescription were carried out to predict its anti-epileptic potential mechanism. RESULTS: A total of 122 acupoint prescriptions were included. The core acupoint prescriptions were Baihui (GV20), Hegu (LI4), Neiguan (PC6), Shuigou (GV26) and Taichong (LR3). 277 potential targets were identified, among which 134 were shared with epilepsy. The core targets were extracted by PPI network topology analysis, including signal transducer and activator of transcription 3, tumor necrosis factor (TNF), interleukin (IL)-6, protein kinase B1, c-Jun N-terminal kinase, brain-derived neurotrophic factor, tumor protein 53, vascular endothelial growth factor A, Caspase-3, epidermal growth factor receptor, etc. The main anti-epileptic pathways of the core acupoints were predicted by KEGG enrichment, including lipid and atherosclerosis, neurodegeneration, phosphatidylinositol-3-kinase/protein B kinase signaling pathway, mitogen-activated protein kinase signaling pathway, cyclic adenosine monophosphate signaling pathway, TNF signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor-1 signaling pathway, apoptosis, etc., involving neuronal death, synaptic plasticity, oxidative stress, inflammation and other related biological process. CONCLUSIONS: The core acupoint prescription of acupuncture and moxibustion intervention for epilepsy can act on multiple targets and multiple pathways to exert anti-epileptic effects, which can provide a theoretical basis for further clinical application and mechanism research.

GraphormerDTI: A graph transformer-based approach for drug-target interaction prediction.

The application of Artificial Intelligence (AI) to screen drug molecules with potential therapeutic effects has revolutionized the drug discovery process, with significantly lower economic cost and time consumption than the traditional drug discovery pipeline. With the great power of AI, it is possible to rapidly search the vast chemical space for potential drug-target interactions (DTIs) between candidate drug molecules and disease protein targets. However, only a small proportion of molecules have labelled DTIs, consequently limiting the performance of AI-based drug screening. To solve this problem, a machine learning-based approach with great ability to generalize DTI prediction across molecules is desirable. Many existing machine learning approaches for DTI identification failed to exploit the full information with respect to the topological structures of candidate molecules. To develop a better approach for DTI prediction, we propose GraphormerDTI, which employs the powerful Graph Transformer neural network to model molecular structures. GraphormerDTI embeds molecular graphs into vector-format representations through iterative Transformer-based message passing, which encodes molecules' structural characteristics by node centrality encoding, node spatial encoding and edge encoding. With a strong structural inductive bias, the proposed GraphormerDTI approach can effectively infer informative representations for out-of-sample molecules and as such, it is capable of predicting DTIs across molecules with an exceptional performance. GraphormerDTI integrates the Graph Transformer neural network with a 1-dimensional Convolutional Neural Network (1D-CNN) to extract the drugs' and target proteins' representations and leverages an attention mechanism to model the interactions between them. To examine GraphormerDTI's performance for DTI prediction, we conduct experiments on three benchmark datasets, where GraphormerDTI achieves a superior performance than five state-of-the-art baselines for out-of-molecule DTI prediction, including GNN-CPI, GNN-PT, DeepEmbedding-DTI, MolTrans and HyperAttentionDTI, and is on a par with the best baseline for transductive DTI prediction. The source codes and datasets are publicly accessible at https://github.com/mengmeng34/GraphormerDTI.

Asiaticoside ameliorates DSS-induced colitis in mice by inhibiting inflammatory response, protecting intestinal barrier and regulating intestinal microecology.

Ulcerative colitis (UC) is one of the most prevalent inflammatory bowel diseases and poses a serious threat to human health. Currently, safe and effective preventive measures are unavailable. In this study, the protective effects of asiaticoside (AS) on dextran sodium sulfate (DSS)-induced colitis in mice and the underlying molecular mechanism were investigated. In this experiment, colitis was induced in mice with DSS. Subsequently, the role of AS in colitis and its underlying mechanisms were examined using H&E staining, immunofluorescence staining, western blot, Elisa, FMT, and other assays. The results showed that AS significantly attenuated the related symptoms of DSS-induced colitis in mice. In addition, AS inhibited the activation of signaling pathways TLR4/NF-κB and MAPK reduced the release of inflammatory factors, thereby attenuating the inflammatory response in mice. AS administration also restored the permeability of the intestinal barrier by increasing the levels of tight junction-associated proteins (claudin-3, occludin, and ZO-1). In addition, AS rebalanced the intestinal flora of DSS-treated mice by increasing the diversity of the flora. AS can alleviate DSS-induced ulcerative colitis in mice by maintaining the intestinal barrier, thus inhibiting the signaling pathways TLR4/NF-κB and MAPK activation, reducing the release of inflammatory factors, and regulating intestinal microecology.

Understanding the molecular mechanisms of Acori Tatarinowii Rhizoma: Nardostahyos Radix et Rhizoma in epilepsy treatment using network pharmacology and molecular docking.

Acori Tatarinowii Rhizoma (ATR) and Nardostahyos Radix et Rhizoma (NRR) are well-known traditional Chinese medicines that have been extensively used for the treatment of epilepsy (EP). However, the precise molecular mechanism of ATR-NRR action remains unclear because of their intricate ingredients. This study aimed to investigate the underlying mechanism of ATR-NRR in EP treatment using network pharmacology and molecular docking techniques. Herbal medicine and disease gene databases were searched to determine active constituents and shared targets of ATR-NRR and EP. A protein-protein interaction network was constructed using the STRING database, while the Gene Ontology and the Kyoto Encyclopedia of Genes and Genome pathway enrichment were performed using R programming. An ingredient-target-pathway network map was constructed using the Cytoscape software, incorporating network topology calculations to predict active ingredients and hub targets. The binding abilities of active ingredients and hub targets were examined using molecular docking. Nine qualified compounds and 53 common targets were obtained. The prominent active compounds were kaempferol, acacetin, cryptotanshinone, 8-isopentenyl-kaempferol, naringenin, and eudesmin, while the primary targets were RELA, AKT1, CASP3, MAPK8, JUN, TNF, and TP53. Molecular docking analysis revealed that they have substantial binding abilities. These 53 targets were found to influence EP by manipulating PI3K-Akt, IL-17, TNF, and apoptosis signaling pathways. The findings of this study indicate that ATR-NRR functions against EP by acting upon multiple pathways and targets, offering a basis for future study.

Antidepressant effects of Parishin C in chronic social defeat stress-induced depressive mice.

ETHNOPHARMACOLOGY RELEVANCE: Parishin C (Par), a prominent bioactive compound in Gastrodia elata Blume with little toxicity and shown neuroprotective effects. However, its impact on depression remains largely unexplored. AIM OF THE STUDY: This study aims to investigate the antidepressant effects of Par using a chronic social defeat stress (CSDS) mouse model and elucidate its molecular mechanisms. MATERIALS AND METHODS: The CSDS-induced depression mouse model was used to evaluate the therapeutic efficacy of Par. The social interaction test (SIT) and sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were conducted to assess the effects of Par on depressive-like behaviours. The levels of corticosterone, neurotransmitters (5-HT, DA and NE) and inflammatory cytokines (IL-1ß, TNF-α, and IL-6) were evaluated by enzyme-linked immunosorbent assay (ELISA). Activation of a microglia was assessed by immunofluorescence labeling Iba-1. The protein expressions of NLRP3, ASC, caspase-1, and IL-6 verified by Western blot. RESULT: Oral administration of Par (4 and 8 mg/kg) and fluoxetine (10 mg/kg, administration significantly ameliorate depression-like behaviors induced by CSDS, as shown by the increase social interaction in SIT, increase sucrose preference in SPT and the decrease immobility in TST and FST. Par administration decreased serum corticosterone level and increased the 5-HT, DA and NE concentration in the hippocampus and prefrontal cortex. Furthermore, Par treatment suppressed microglial activation (Iba1) as well as reduced levels of IL-1ß, TNF-α, and IL-6) with decreased protein expressions of NLRP3, ASC, caspase-1, and IL-6. CONCLUSIONS: our study provides the first evidence that Par exerts antidepressant-like effects in mice with CSDS-induced depression. This effect appears to be mediated by the normalization of neurotransmitter and corticosterone levels, inhibition of NLRP3 inflammasome activation. This newfound antidepressant property of Par offers a novel perspective on its pharmacological effects, providing valuable insights into its potential therapeutic and preventive applications in depression treatment.

Antioxidation and Hepatoprotection of Selenium Mycelium Polysaccharides Against Alcoholic Liver Diseases from the Cultivated Morel Mushroom Morchella esculenta (Ascomycota).

The liver was regarded as the most important metabolic and detoxification organ in vivo, and Morchella esculenta had been reported as the admittedly rare edible fungus belonging to Ascomycetes contributing to the abundant bioactivities. The objective of this study aimed to confirm the potential antioxidant activities of selenium mycelium polysaccharides (Se-MIP) from M. esculenta against alcoholic liver diseases (ALD) in mice. The results indicated that a selenium concentration of 25 µg/mL exhibited potential in vitro antioxidant capacities of Se-MIP. The in vivo mice results demonstrated that Se-MIP showed potential anti-ALD effects by improving the antioxidant activities and alleviating the hepatic dysfunctions. The present conclusions suggested that Se-MIP could be used as a candidate on improving ALD and its complications for further clinical investigations.

Alpha-lipoic acid supplementation reverses the declining quality of oocytes exposed to cyclophosphamide.

Cyclophosphamide (CY) is a chemotherapeutic drug that is commonly used to treat malignancies of the ovary, breast, and hematology, as well as autoimmune disorders. As a cofactor of mitochondrial multienzyme complexes, alpha lipoic acid (ALA) is well known for its antioxidant characteristics, which operate directly on the scavenging of reactive oxygen species (ROS) and indirectly on the intracellular recycling of other antioxidants. However, the underlying mechanisms through which CY exerts its toxic effects on meiosis and oocyte quality, as well as a viable approach for protecting oocyte quality and preserving fertility, remain unknown. In present study, immunostaining and fluorescence intensity quantification were applied to assess the effects of CY and ALA supplementation on the key processes during the oocyte meiotic maturation. Our results show that supplementing oocytes with ALA, a well-known antioxidant and free radical scavenger, can reverse CY-induced oocyte meiotic maturation failure. Specifically, we found that CY exposure caused oocyte meiotic failure by disrupting meiotic organelle dynamics and arrangement, as well as a prominently impaired cytoskeleton assembly. In addition, CY caused an abnormal distribution of mitochondrion and cortical granules, two indicators of oocyte cytoplasmic maturation. More importantly, we show that ALA supplementation effectively reverses CY-induced meiotic failure and oocyte quality decline by suppressing oxidative stress-induced DNA damage and apoptosis in oocytes. Collectively, our data reveal that ALA supplementation is a feasible approach to protect oocytes from CY-exposed deterioration, providing a better understanding of the mechanisms involved in chemotherapy-induced meiotic failure.

Mechanisms of DHEA-induced AMH increase in the ovarian tissues of PCOS rat.

The present study aimed to build a DHEA-induced polycystic ovary syndrome (PCOS) rat model to evaluate the potential mechanism of DHEA-induced AMH rise in these rat ovarian tissues. A total of 36 female 3-week-old rats were allocated into two groups at random. The control group received merely the same amount of sesame oil for 20 days while the experimental group received 0.2 mL of sesame oil Plus DHEA 6 mg/100 g daily. Both groups' vaginal opening times were noted, and vaginal smears were taken. By using RT-qPCR and Western blot, the mRNA and protein expression of AMH, GATA4, SF1, and SOX9 in the ovarian tissues of the two groups was investigated.The rats in the experimental group appeared to have obvious disorders of the estrus cycle, as evidenced by the ratio of estrus being significantly higher than that in the control group (P < 0.05); HE staining revealed that the ovarian volume, follicular vacuoles, and follicular lumen of the rats in the experimental group increased significantly.The ELISA results revealed that T and AMH in the experimental group were higher than those in the control group at day 15 and 20. AMH、GATA4 and SF1 mRNA and protein expression were higher in the experimental group than in the control group on day 15 and 20 (P < 0.05). On day 20, the experimental group outperformed the control group (P < 0.05). In the DHEA-induced PCOS rat model, androgen may have enhanced AMH expression via increasing the expression of genes associated to the AMH promoter binding site (GATA4, SF1, SOX9).

The effect of music intervention on sedation in elderly patients undergoing transurethral resection of prostate under spinal anesthesia: a prospective randomized controlled clinical trial.

PURPOSE: Music intervention is commonly used as a non-pharmacologic therapeutic modality to alleviate anxiety in perioperative patients. This study aimed to assess the sedative and anxiolytic effects of music on elderly patients receiving transurethral resection of prostate (TURP) under spinal anesthesia. METHODS: This was a prospective randomized controlled trial on patients who aged over 60 and received TURP under spinal anesthesia. Participants were randomized to the music group or the control group (no music). The primary outcome was perioperative BIS values, and the secondary outcomes were patient's perioperative anxiety levels, heart rate (HR), blood pressure, and patient satisfaction score. RESULTS: A total of 82 patients were analyzed. The perioperative BIS values in the music group were significantly lower than those of the control group at almost all time points (P < 0.001), as well as showed a significant reduction compared with baseline (P < 0.001), whereas the control group did not. In comparison with the control group, systolic blood pressure (SBP) significantly decreased in the music group at the beginning (mean difference, - 8.0 mmHg; 95% CI - 15.70 to 0.35; P = 0.041) and the 60th minute (mean difference, - 7.9 mmHg; 95% CI - 15.30 to 0.51; P = 0.037) of TURP. Furthermore, compared with baseline within the music group, diastolic blood pressure (DBP) and HR significant reduced at whole time points (P < 0.05), yet the control group not. CONCLUSION: Music intervention effectively provided slight sedation for elderly patients when undergoing TURP under spinal anesthesia without sedatives.

The efficacy of Chinese herbal ointment in treating perianal eczema: A systematic review and meta-analysis.

BACKGROUND: Traditional Chinese herbal ointment has significant curative effect and few side effects in the treatment of perianal eczema (PE). Currently, there is no systematic evaluation on the treatment of PE with traditional Chinese medicine ointment. The current aim is to systematically evaluate the efficacy of traditional Chinese medicine ointment in the treatment of PE through meta-analysis. METHODS: Randomized controlled trials on the treatment of PE with Chinese herbal plaster were included in the meta-analysis, which was searched in Chinese and English databases up to March 1, 2023. The search will be conducted in accordance with the object of PICOS framework. Two research will independently use EndnoteX9 to extract the data and evaluate the quality assessment of included trails. Meta-analysis was performed using Revman5.4.1 provided by Cochrane Collaboration; when the outcome indicator is a dichotomous variable, relative risk (RR) was used as the effect size; when the outcome indicator is a continuous variable, weighted mean difference (MD) was used as the effect size, each effect size should be expressed as 95% confidence interval (CI). RESULTS: The results of meta-analysis showed that: The total effective rate of PE (RR: 1.22, 95% CI: 1.15, 1.30, P < .01; I2 = 32%, Q = 0.17). The cure rate of PE (RR: 3.37, 95% CI: 2.30, 4.94, P < .01; I2 = 21% Q = 0.26). The recurrence rate of PE (RR: 0.25, 95% CI: 0.13, 0.48, P < .01; I2 = 31%Q = 0.23). Itchy points (MD: 0.04, 95% CI: -0.19, 0.27; I2 = 26%) Skin damage area (MD: -0.37, 95% CI: -0.56, -0.19; I2 = 26%). Skin damage form (MD: -0.59, 95% CI: -0.81. -0.36; I2 = 0%). CONCLUSION: A total of 11 articles were included in this study for meta-analysis, and the results showed that Chinese medicine ointment is more helpful in improving the skin lesion area and skin damage form, significantly improve the response rate and cure rate, reduce the recurrence rate. Chinese herbal ointment has guiding significance for clinical practice which deserve to use ointments by further experimental and clinical investigation.

Fresh Gastrodia elata Blume alleviates simulated weightlessness-induced cognitive impairment by regulating inflammatory and apoptosis-related pathways.

In aerospace medicine, the influence of microgravity on cognition has always been a risk factor threatening astronauts' health. The traditional medicinal plant and food material Gastrodia elata Blume has been used as a therapeutic drug for neurological diseases for a long time due to its unique neuroprotective effect. To study the effect of fresh Gastrodia elata Blume (FG) on cognitive impairment caused by microgravity, hindlimb unloading (HU) was used to stimulate weightlessness in mice. The fresh Gastrodia elata Blume (0.5 g/kg or 1.0 g/kg) was intragastrically administered daily to mice exposed to HU and behavioral tests were conducted after four weeks to detect the cognitive status of animals. The behavioral tests results showed that fresh Gastrodia elata Blume therapy significantly improved the performance of mice in the object location recognition test, Step-Down test, and Morris Water Maze test, including short-term and long-term spatial memory. According to the biochemical test results, fresh Gastrodia elata Blume administration not only reduced serum factor levels of oxidative stress but also maintained the balance of pro-inflammatory and anti-inflammatory factors in the hippocampus, reversing the abnormal increase of NLRP3 and NF-κB. The apoptosis-related proteins were downregulated which may be related to the activation of the PI3K/AKT/mTOR pathway by fresh Gastrodia elata Blume therapy, and the abnormal changes of synapse-related protein and glutamate neurotransmitter were corrected. These results identify the improvement effect of fresh Gastrodia elata Blume as a new application form of Gastrodia elata Blume on cognitive impairment caused by simulated weightlessness and advance our understanding of the mechanism of fresh Gastrodia elata Blume on the neuroprotective effect.

GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet are involved in itch processing in mice.

Itch and pain are two closely related sensations that receiving similar encodings at multiple levels. Accumulated evidences suggest that activation of the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL)-to-lateral and ventrolateral periaqueductal gray (l/vlPAG) projections mediates the antinociceptive effects of bright light therapy. Clinical study showed that bright light therapy may ameliorate cholestasis-induced pruritus. However, the underlying mechanism and whether this circuit participates in itch modulation remains unclear. In this study, chloroquine and histamine were utilized to induce acute itch models in mice. Neuronal activities in vLGN/IGL nucleus were evaluated with c-fos immunostaining as well as fiber photometry. Optogenetic manipulations were performed to activate or inhibit GABAergic neurons in the vLGN/IGL nucleus. Our results showed that the expressions of c-fos in vLGN/IGL were significantly increased upon both chloroquine- and histamine-induced acute itch stimuli. GABAergic neurons in vLGN/IGL were activated during histamine and chloroquine-induced scratching. Optogenetic activation of the vLGN/IGL GABAergic neurons exerts antipruritic effect, while inhibiting these neurons exerts pruritic effect. Our results provide evidence that GABAergic neurons in vLGN/IGL nucleus might play a crucial role in modulating itch, which may provide clue for application of bright light as an antipruritic treatment in clinic.

The alcohol extracts of Sceptridium ternatum (Thunb.) Lyon exert anti-pulmonary fibrosis effect through targeting SETDB1/STAT3/p-STAT3 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is a pathological process of irreversible scarring of lung tissues, with limited treatment means. Sceptridium ternatum (Thunb.) Lyon (STE) is a traditional Chinese herbal medicine that has a traditional use in relieving cough and asthma, resolving phlegm, clearing heat, and detoxicating in China. However, its role in PF has not been reported. AIM OF THE STUDY: This study aims to investigate the protective role of STE in PF and the underlying mechanisms. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were divided into control group, PF model group, positive drug (pirfenidone) group and STE group. After 28 days of STE administration in bleomycin (BLM)-induced PF rats, living Nuclear Magnetic Resonance Imaging (NMRI) was used to observe the structural changes of lung tissues. H&E and Masson's trichrome staining were used to observe PF-associated pathological alteration, and immunohistochemistry (IHC) staining, western blotting, and qRT-PCR were used to detect the expression of PF-related marker proteins in the lung tissues. ELISA was used to detect PF-associated biochemical criteria in the lung tissue homogenates. The proteomics technology was used to screen the different proteins. Co-immunoprecipitation, western blotting, and IHC staining were used to confirm the underlying targets of STE as well as its downstream signaling. UPLC-Triple-TOF/MS assay was used to explore the effective components in the alcohol extracts of STE. Autodock vina was used to detect the potential binding between the above effective components and SETDB1. RESULTS: STE prevented PF by inhibiting the activation of lung fibroblasts and ECM deposition in BLM-induced PF rats. Mechanism analyses demonstrated that STE could inhibit the up-regulation of SETDB1 induced by BLM and TGF-ß1, which further blocked the binding of SETDB1 and STAT3 as well as the phosphorylation of STAT3, ultimately preventing the activation and proliferation of lung fibroblasts. CONCLUSION: STE played a preventive role in PF by targeting the SETBD1/STAT3/p-STAT3 pathway, which may be a potential therapeutic agent for PF.

Lonp1 and Sig-1R contribute to the counteraction of ursolic acid against ochratoxin A-induced mitochondrial apoptosis.

Ochratoxin A (OTA), a secondary fungal metabolite with nephrotoxicity, is widespread in numerous kinds of feeds and foodstuffs. Ursolic acid (UA), a water-insoluble pentacyclic triterpene acid, exists in a wide range of food materials and medicinal plants. Our earlier researches provided preliminary evidence that mitochondria- and mitochondria-associated endoplasmic reticulum membranes (MAMs)-located stress-responsive Lon protease 1 (Lonp1) had a protective function in OTA-induced nephrotoxicity, and the renoprotective function of UA against OTA partially due to Lonp1. However, whether other MAMs-located protiens, such as endoplasmic reticulum stress (ERS)-responsive Sigma 1-type opioid receptor (Sig-1R), contribute to the protection of UA against OTA-induced nephrotoxicity together with Lonp1 needs further investigation. In this study, the cell viability, reactive oxygen species, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells varied with OTA and/or UA/CDDO-me/AVex-73/Sig-1R siRNA treatments were determined. Results indicated that a 24 h-treatment of 5 µM OTA could significantly induce mitochondrial-mediated apoptosis via repressing Lonp1 and Sig-1R, thereby enhancing the protein expressions of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α, and Bax, and inhibiting the protein expression of Bcl-2 in HK-2 cells, which could be remarkably relieved by a 2 h-pre-treatment of 4 µM UA (P < 0.05). In conclusion, through mutual promotion between Lonp1 and Sig-1R, UA could effectively relieve OTA-induced apoptosis in vitro and break the vicious cycle between oxidative stress and ERS, which activated the mitochondrial apoptosis pathway.

Identification of NPF Family Genes in Brassica rapa Reveal Their Potential Functions in Pollen Development and Response to Low Nitrate Stress.

Nitrate Transporter 1/Peptide Transporter Family (NPF) genes encode membrane transporters involved in the transport of diverse substrates. However, little is known about the diversity and functions of NPFs in Brassica rapa. In this study, 85 NPFs were identified in B. rapa (BrNPFs) which comprised eight subfamilies. Gene structure and conserved motif analysis suggested that BrNFPs were conserved throughout the genus. Stress and hormone-responsive cis-acting elements and transcription factor binding sites were identified in BrNPF promoters. Syntenic analysis suggested that tandem duplication contributed to the expansion of BrNPFs in B. rapa. Transcriptomic profiling analysis indicated that BrNPF2.6, BrNPF2.15, BrNPF7.6, and BrNPF8.9 were expressed in fertile floral buds, suggesting important roles in pollen development. Thirty-nine BrNPFs were responsive to low nitrate availability in shoots or roots. BrNPF2.10, BrNPF2.19, BrNPF2.3, BrNPF5.12, BrNPF5.16, BrNPF5.8, and BrNPF6.3 were only up-regulated in roots under low nitrate conditions, indicating that they play positive roles in nitrate absorption. Furthermore, many genes were identified in contrasting genotypes that responded to vernalization and clubroot disease. Our results increase understanding of BrNPFs as candidate genes for genetic improvement studies of B. rapa to promote low nitrate availability tolerance and for generating sterile male lines based on gene editing methods.

Tenuifolin ameliorates the sleep deprivation-induced cognitive deficits.

Tenuifolin (TEN), a natural neuroprotective compound obtained from the Polygala tenuifolia Willd plant, has improved cognitive symptoms. However, the impact of TEN on memory impairments caused by sleep deprivation (SD) is unclear. Accordingly, the objective of this study was to investigate the mechanisms behind the preventative benefits of TEN on cognitive impairment caused by SD. TEN (10 and 20 mg/kg) and Huperzine A (0.1 mg/kg) were given to mice through oral gavage for 28 days during the SD process. The results indicate that TEN administrations improve short- and long-term memory impairments caused by SD in the Y-maze, object identification, and step-through tests. Moreover, TEN stimulated the generation of anti-inflammatory cytokines (interleukin-10), lowered the production of pro-inflammatory cytokines (interleukin-1ß, interleukin-6, and interleukin-18), and activated microglia, improving antioxidant status in the hippocampus. TEN treatments significantly boosted the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 while considerably decreasing the expression of NOD-like receptor thermal protein domain associated protein 3 and caspase-1 p20. Additionally, TEN restored the downregulation of the brain-derived neurotrophic factor signaling cascade and the impaired hippocampal neurogenesis induced by SD. When considered collectively, our data suggest that TEN is a potentially effective neuroprotective agent for cognition dysfunction.

Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway.

OBJECTIVE: To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy. METHODS: H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells. RESULTS: Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05). CONCLUSION: Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.

Post-diagnostic Zinc Supplement Use and Prostate Cancer Survival Among Men With Nonmetastatic Prostate Cancer.

PURPOSE: Biological and experimental evidence support restoration of normal zinc levels in malignant prostate cells as a promising prostate cancer treatment, yet the influence of zinc supplementation after diagnosis on prostate cancer survival in a human population is unknown. MATERIALS AND METHODS: We prospectively assessed post-diagnostic zinc supplementation in relation to prostate cancer survival among 5,788 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2019). We used Cox regression models to estimate the multivariable hazard ratios and 95% confidence intervals of lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality according to post-diagnostic zinc supplement use and dosage. RESULTS: During a median follow-up of 11 years, we documented 527 lethal prostate cancer events and 3,198 all-cause deaths. Fifteen percent of men reported zinc supplement use post-diagnosis. Compared to nonusers, post-diagnostic zinc supplement use was associated suggestively with a lower risk of lethal prostate cancer (HR [95% CI], 0.82 [0.60-1.13]) and significantly with all-cause mortality (0.84 [0.74-0.96]). The inverse association was mostly observed among men who used post-diagnostic zinc supplements of 1-24 mg/d (lethal prostate cancer: 0.55 [0.32-0.96]; all-cause mortality: 0.77 [0.64-0.93]), while higher dosage did not show a lower risk. CONCLUSIONS: Post-diagnostic low-dose zinc supplement use among nonmetastatic prostate cancer patients was associated with lower risk of lethal prostate cancer and all-cause mortality. A potential benefit of low-dose post-diagnostic zinc supplement for prostate cancer survival merits further study.

English Learning Stress, Self-Efficacy, and Burnout among Undergraduate Students: The Moderating Effect of Mindfulness and Gender.

Research has indicated that English learning stress contributes significantly to English learning burnout among undergraduate students. However, knowledge of the mediating and moderating mechanisms underlying this relationship is limited. To bridge this gap, a moderated mediation model was constructed to examine whether English learning self-efficacy mediated the relationship between English learning stress and English learning burnout. Furthermore, this study analyzed whether the mediated relationship was moderated by mindfulness and gender. A total of 1130 Chinese undergraduate students (mean age = 20.84 years, SD = 1.57 years) reported their experiences regarding English learning stress, English learning self-efficacy, English learning burnout, and mindfulness. After controlling for covariates, the results revealed that English learning self-efficacy mediated the positive link between English learning stress and English learning burnout among both men and women. Moreover, the findings demonstrated that the indirect link was moderated by mindfulness among male undergraduate students. However, the moderating effect of mindfulness was not significant among the women in this study. The implications of these findings for future research, and the development of intervention and prevention of English learning burnout are discussed.

Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study.

BACKGROUND: Zinc supplementation was hypothesized to have therapeutic potential against prostate cancer, but its influence on prostate cancer incidence especially at high doses is controversial. METHODS: A total of 47,240 men from the Health Professionals Follow-up Study were followed from 1986 to 2016. Men reported their zinc supplement use at baseline and biennially thereafter. Clinical features of prostate cancer included stage, grade, lethal and aggressive (T4 or N1 or M1 or Gleason 8-10) outcome. Multivariable Cox proportional hazards models were used to evaluate the association between zinc supplement use and incidence of prostate cancer. RESULTS: During a median follow-up of 28.3 years, we documented 6,980 incident prostate cancer cases including 1,053 lethal and 1,143 aggressive. Zinc supplement use was not associated with overall, localized, low- and intermediate-grade prostate cancer. However, compared to never-users, men who used supplement zinc more than 75 mg/day were at higher risk for lethal (HR: 1.76, 95% CI: 1.16-2.66, Ptrend = 0.001) and aggressive prostate cancer (HR: 1.80, 95% CI: 1.19-2.73, Ptrend = 0.006). Similarly, men who took supplemental zinc for 15 or more years had a higher risk for lethal (HR: 1.91, 95% CI: 1.28-2.85, Ptrend <0.001) and aggressive prostate cancer (HR: 1.55, 95% CI: 1.03-2.33, Ptrend = 0.004). CONCLUSION: Zinc supplementation of more than 75 mg per day or over 15 years may substantially increase risk of lethal and aggressive prostate cancer. Caution is warranted regarding excessive usage of zinc supplements among adult men.