Natural product Kaji-ichigoside F1 exhibits rapid antidepression via activating the AMPA-BDNF-mTOR pathway and inhibiting the NMDAR-CaMKIIα pathway.

BACKGROUND: Depression is a common and recurrent neuropsychiatric disorder. Recent studies have shown that the N-methyl-d-aspartate (NMDA) receptor (NMDAR) is involved in the pathophysiology of depression. Previous studies have found that Kaji-ichigoside F1 (KF1) has a protective effect against NMDA-induced neurotoxicity. However, the antidepressant mechanism of KF1 has not been confirmed yet. PURPOSE: In the present study, we aimed to evaluate the rapid antidepressant activity of KF1 and explore the underlying mechanism. STUDY DESIGN: First, we explored the effect of KF1 on NMDA-induced hippocampal neurons and the underlying mechanism. Second, depression was induced in C57BL/6 mice via chronic unpredictable mild stress (CUMS), and the immediate and persistent depression-like behavior was evaluated using the forced swimming test (FST) after a single administration of KF1. Third, the contributions of NMDA signaling to the antidepressant effect of KF1 were investigated using pharmacological interventions. Fourth, CUMS mice were treated with KF1 for 21 days, and then their depression-like behaviors and the underlying mechanism were further explored. METHODS: The FST was used to evaluate immediate and persistent depression-like behavior after a single administration of KF1 with or without NMDA pretreatment. The effect of KF1 on depressive-like behavior was investigated in CUMS mice by treating them with KF1 once daily for 21 days through the sucrose preference test, FST, open field test, and tail suspension test. Then, the effects of KF1 on the morphology and molecular and functional phenotypes of primary neuronal cells and hippocampus of mice were investigated by hematoxylin-eosin staining, Nissl staining, propidium iodide staining, TUNEL staining, Ca2+ imaging, JC-1 staining, ELISA, immunofluorescence analysis, RT-PCR, and Western blot. RESULTS: KF1 could effectively improve cellular viability, reduce apoptosis, inhibit the release of LDH and Ca2+, and increase the mitochondrial membrane potential and the number of dendritic spines numbers in hippocampal neurons. Moreover, behavioral tests showed that KF1 exerted acute and sustained antidepressant-like effects by reducing Glu-levels and ameliorating neuronal damage in the hippocampus. Additionally, in vivo and in vitro experiments revealed that PSD95, Syn1, α-amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and brain-derived neurotrophic factor (BDNF) were upregulated at the protein level, and BDNF and AMPA were upregulated at the mRNA level. NR1 and NR2A showed the opposite trend. CONCLUSION: These results confirm that KF1 exerts rapid antidepressant effects mainly by activating the AMPA-BDNF-mTOR pathway and inhibiting the NMDAR-CaMKIIα pathway. This study serves as a new reference for discovering rapid antidepressants.

Rhein alleviates myocardial ischemic injury by inhibiting mitochondrial division, activating mitochondrial autophagy and suppressing myocardial cell apoptosis through the Drp1/Pink1/Parkin pathway.

BACKGROUND: Rhein, which has antioxidant and anti-inflammatory response properties, is a beneficial treatment for different pathologies. However, the mechanism by which rhein protects against myocardial ischemic injury is poorly understood. METHODS AND RESULTS: To establish an acute myocardial infarction (AMI) rat model, we performed left anterior descending (LAD) ligation. Sprague‒Dawley rats were randomly divided into four groups: sham, AMI, AMI + rhein (AMI + R), and AMI + mitochondrial fission inhibitor (AMI + M). The extent of myocardial injury was evaluated by TTC staining, serum myocardial injury markers, and HE and Masson staining. Cardiac mitochondria ultrastructure was visualized by transmission electron microscopy. TUNEL assay and flow cytometry analysis were used to estimate cell apoptosis. Protein expression levels were measured by Western blotting. In vitro, the efficacy of rhein was assessed in H9c2 cells under hypoxic condition. Our results revealed that rats with AMI exhibited increased infarct size and indicators of myocardial damage, along with activation of Drp1-dependent mitochondrial fission, decreased mitophagy and increased apoptosis rates. However, pretreatment with rhein significantly reversed these effects and demonstrated similar efficacy to Mdivi-1. Furthermore, rhein pretreatment protected against myocardial ischemic injury by inhibiting mitochondrial fission, as evidenced by decreased Drp1 expression. It also enhanced mitophagy, as indicated by increased expression of Beclin1, Pink1 and Parkin, an increased LC3-II/LC3-I ratio and increased formation of autolysosomes. Additionally, rhein pretreatment mitigated apoptosis in AMI. These results were also confirmed in vitro in H9c2 cells. CONCLUSION: Our results demonstrate that rhein pretreatment exerts cardioprotective effects against myocardial ischemic injury via the Drp1/Pink1/Parkin pathway.

Effect of acupuncture pretreatment on inflammatory response of exercise-induced skeletal muscle damage in rats based on TLR9/MyD88/NF-κB signaling pathway. / 基于TLR9/MyD88/NF­κBä¿¡å·é€šè·¯æŽ¢è®¨é’ˆåˆºé¢„å¤„ç†å¯¹è¿åŠ¨æ€§éª¨éª¼è‚ŒæŸä¼¤å¤§é¼ ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of acupuncture pretreatment on toll-like receptor 9/myeloid differentiation factor 88/nuclear factor-κB (TLR9/MyD88/NF-κB) signaling pathway and inflammatory response in the rats with exercise-induced skeletal muscle damage (EIMD) and explore the underlying mechanism of this pretreatment for EIMD. METHODS: A total of 88 male SD rats were randomly divided into a blank group (8 rats), a model group (40 rats) and an acupuncture pretreatment group (40 rats). In the model group and the acupuncture pretreatment group, 5 subgroups were randomized according to the sampling time of 0, 12, 24, 48 and 72 h of modeling, with 8 rats in each one, respectively. Before modeling, in the acupuncture pretreatment group, acupuncture was delivered at bilateral "Zusanli" (ST 36) and "Guanyuan" (CV 4) for 20 min, once daily for consecutive 7 days. By one-time intermittent downhill centrifugal exercise on animal experimental treadmill, EIMD model was established in the model group and the acupuncture pretreatment group. The ultrastructure of gastrocnemius muscle was observed under transmission electron microscope. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum were detected by ELISA. The protein and mRNA expression of TLR9, MyD88 and NF-κB p65 in the gastrocnemius tissue of rats was detected by the Western blot and real-time PCR, respectively. RESULTS: Compared with the blank group, the gastrocnemius ultrastructure in the model group showed the damage of different degrees, with myofilaments disarranged and twisted, mitochondria obviously swollen and mitochondrial crista partially defected. Compared with the model group, the injury was mild, most of muscle fibers were arranged neatly and the number of mitochondria increased remarkably in the acupuncture pretreatment group. Compared with the blank group, in the model group, the serum IL-6 levels increased at 0, 12, 24 and 48 h after modeling in the rats (P<0.01), and TNF-α levels were elevated at each time point after modeling (P<0.05, P<0.01). In the acupuncture pretreatment group, the serum IL-6 levels were reduced at 12, 24 and 48 h after modeling (P<0.01, P<0.05), and the TNF-α levels decreased at 24, 48 and 72 h after modeling (P<0.01) when compared with those in the model group at the same time points separately. The serum IL-6 and TNF-α levels ascended and then tended to decline in the model group and the acupuncture pretreatment group. Compared with the blank group, the protein and mRNA expression of TLR9 and NF-κB p65 in the gastrocnemius tissue increased at 12, 24, 48 and 72 h after modeling (P<0.01, P<0.05), and the protein and mRNA expression levels of MyD88 in the gastrocnemius tissue at each time point after modeling were elevated (P<0.05, P<0.01) in the model group. When compared with the model group at the same time points, in the acupuncture pretreatment group, the protein expression of TLR9 in the gastrocnemius tissue decreased at 12, 24, 48 and 72 h after modeling (P<0.05, P<0.01), and the mRNA expression of TLR9 was declined at 24, 48 and 72 h after modeling (P<0.01, P<0.05); the protein and mRNA expression of MyD88 in the gastrocnemius decreased at 24, 48 and 72 h after modeling (P<0.01, P<0.05), and that of NF-κB p65 was reduced at 24 h and 48 h after modeling (P<0.01). The protein and mRNA expression of TLR9, MyD88 and NF-κB p65 in the gastrocnemius tissue showed a trend of decrease after increase in the model group and the acupuncture pretreatment group. CONCLUSIONS: Acupuncture pretreatment can alleviate exercise-induced skeletal muscle damage, which may be related to modulating the expression of TLR9/MyD88/NF-κB signaling pathway to inhibit the inflammatory response.

Development and application of the practical training instrument of warming needle moxibustion with quantifiable evaluation. / ä¸€ç§å¯é‡åŒ–è¯„ä»·çš„æ¸©é’ˆç¸å®žè®­æ•™å­¦ä»ªçš„ç ”åˆ¶ä¸Žå®žè·µ.

Based on summarizing the essential procedures and elements of traditional manipulation techniques of warming needle moxibustion and determining the quantitative parameters and indicators for evaluating the operation of this acupuncture technique, a training instrument of warming needle moxibustion was developed and adopted in the curriculum teaching of practice. It showed that this instrument could quantify the speed of fixing mugwort ball on the needle handle, the number of the prepared mugwort ball, the duration for anti-vibration, the frequency of anti-vibration and the burning time of mugwort ball. The instrument could objectively evaluate the skills of warming needle moxibustion and the effects of fixing mugwort ball. Besides, it may provide the references to improve the protocol of the future research. The development and application of the practical training instrument of warming needle moxibustion is conductive to cultivate the standardization and accuracy of the technique operation in students, and it is significant for objectif-ying the teaching course of warming needle and teaching assessment, as well as for diversifying the teaching modes. Moreover, it plays an exemplary role in the practical training of other acupuncture and moxibustion techniques.

Inhibitory effect of Incarvillea diffusa Royle extract in the formation of calcium oxalate nephrolithiasis by regulating ROS-induced Nrf2/HO-1 pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate (CaOx) kidney stones are widely acknowledged as the most prevalent type of urinary stones, with high incidence and recurrence rates. Incarvillea diffusa Royle (ID) is a traditionally used medicinal herb in the Miao Minzu of Guizhou province, China, for treating urolithiasis. However, the active components and the underlying mechanism of its pharmacodynamic effects remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential inhibitory effect of the active component of ID on the formation of CaOx nephrolithiasis and elucidate the underlying mechanism. MATERIALS AND METHODS: In vivo, a CaOx kidney stone model was induced in Sprague-Dawley (SD) rats using an ethylene glycol and ammonium chloride protocol for four weeks. Forty-eight male SD rats were randomly assigned to 6 groups (n = 8): blank group, model group, apocynin group, and low, medium, and high dose of ID's active component (IDW) groups. After three weeks of administration, rat urine, serum, and kidney tissues were collected. Renal tissue damage and crystallization, Ox, BUN, Ca2+, CRE, GSH, MDA, SOD contents, and levels of IL-1ß, IL-18, MCP-1, caspase-1, IL-6, and TNF-α in urine, serum, and kidney tissue were assessed using HE staining and relevant assay kits, respectively. Protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in kidney tissues was quantified via Western blot. The antioxidant capacities of major compounds were evaluated through DPPH, O2·-, and ·OH radical scavenging assays, along with their effects on intracellular ROS production in CaOx-induced HK-2 cells. RESULTS: We found that IDW could significantly reduce the levels of CRE, GSH, MDA, Ox, and BUN, and enhancing SOD activity. Moreover, it could inhibit the secretion of TNF-α, IL-1ß, IL-18, MCP-1, caspase-1, and decreased protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in renal tissue. Three major compounds isolated from IDW exhibited promising antioxidant activities and inhibited intracellular ROS production in CaOx-induced HK-2 cells. CONCLUSIONS: IDW facilitated the excretion of supersaturated Ca2+ and decreased the production of Ox, BUN in SD rat urine, and mitigated renal tissue damage by regulating Nrf2/HO-1 signaling pathway. Importantly, the three major compounds identified as active components of IDW contributed to the inhibition of CaOx nephrolithiasis formation. Overall, IDW holds significant potential for treating CaOx nephrolithiasis.

From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

Molecular mechanisms of Chengshi Beixie Fenqing Decoction based on network pharmacology: pivotal roles of relaxin signaling pathway and its associated target proteins against Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease that affects the quality of life of middle-aged and older men. We investigated the therapeutical effects of Chengshi Beixie Fenqing Decoction (CBFD), a classic traditional Chinese medicine prescription, on BPH through in vivo model and network pharmacology. Bioactives in CBFD were detected through UPLC-Q-Tof-MS/MS and GC-MS, and filtered by the modified Lipinski's rule. Target proteins associated with the filtered compounds and BPH are selected from public databases. Venn diagram identified the overlapping target proteins between the bioactives-interacted target proteins and the BPH-targeted proteins. The bioactive-protein interactive networking of BPH was analyzed through the KEGG pathway on STRING to identify potential ligand-target and visualized the rich factors on the R packet. After that, the molecular docking test (MDT) was performed between bioactives and target proteins. It showed that the mechanism of CBFD against BPH was related to 104 signaling pathways of 42 compounds. AKT1, 6-demethyl-4'-methyl-N-methylcoclaurine and relaxin signaling pathways were selected as a hub target, key bioactivitie and hub signaling pathway, respectively. In addition, three major compounds, 6-demethyl-4'-methyl-N-methylcoclaurine, isoliensinine and liensinine, had the highest affinity on MDT for the three crucial target proteins, AKT1, JUN and MAPK1. These proteins were associated with the relaxin signaling pathway, which regulated the level of nitric oxide and is implicated in both BPH development and CBFD. We concluded that the three key bioactivities found in Plumula nelumbinis of CBFD may contribute to improving BPH condition by activating the relaxin signaling pathways.Communicated by Ramaswamy H. Sarma.

Magnolol supplementation alleviates diquat-induced oxidative stress via PI3K-Akt in broiler chickens.

This experiment was conducted to investigate the effects of magnolol on the oxidative parameters and jejunum injury induced by diquat in broiler chickens. This test adopts a 2 × 2 factors design, a total of 288 one-day-old male AA broiler chicks randomly allocated to four groups, consisting of six replicates of 12 birds each, which was then denoted as CON group, diquat (DIQ) group (16 mg/kg BW diquat was injected into birds at the age of 21 days), magnolol (MAG) group (basic bird diet supplemented with 300 mg/kg magnolol), and MAG + DIQ group. At 21 days of age, broilers in the DIQ group and the MAG + DIQ group were intraperitoneally injected with 16 mg/kg BW diquat. Results showed that diet supplementing with MAG could alleviate the decrease of ADG to a certain extent after exposure to DIQ. Addition of magnolol to the diet alleviated the decrease of ADG during injection, antioxidant enzymes, and gene expression and increased the markers of oxidative damage induced by diquat induction. Magnolol supplement reversed the increase of apoptotic cells in the diquat-induced chicken jejunum. RNA sequencing showed that PI3K-Akt, calcium, and NF-kappa B signaling pathways were the main enrichment pathways between the DIQ group and the MAG + DIQ group. Our findings revealed that magnolol may improve antioxidant enzyme activity and expression of related genes through the PI3K-Akt pathway to alleviate oxidative stress.

Effect of mild moxibustion with moxa stick and infrared mild moxibustion on skin blood perfusion at Waiguan (TE 5). / è‰¾æ¡æ¸©å’Œç¸ä¸Žçº¢å¤–çº¿æ¸©å’Œç¸å¯¹å¤–å ³ç©´çš®è‚¤è¡€æµçŒæ³¨é‡çš„å½±å“.

OBJECTIVES: To observe the changes of skin blood flow perfusion at Waiguan (TE 5) caused by mild moxibustion with moxa stick and infrared mild moxibustion using laser speckle contrast imaging technology, and to compare the microcirculatory effect during and after both moxibustion methods and explore the dose-response relationship of moxibustion. METHODS: Twenty-four healthy participants were treated with mild moxibustion with moxa stick and infrared mild moxibustion at left Waiguan (TE 5). The record started when the skin temperature reached (44±1) °C, and both moxibustion methods were provided within this temperature range. The 20-minute moxibustion process was divided into four stages (5, 10, 15, and 20 min) using interpolation method, and each participant completed eight interventions with a minimum 24-hour interval between different interventions. The skin surface temperature of the left Waiguan (TE 5) was monitored when both moxibustion interventions were given for 10 min using a TES1306 thermocouple thermometer. The skin microcirculatory blood perfusion units (MBPU) of left Waiguan (TE 5) was measured using a PSIN-01087 laser speckle blood flow imager 1 min before moxibustion, at 5, 10, 15, 20 min during moxibustion and continuously for 20 min after moxibustion in each intervention. RESULTS: The skin surface temperature of the left Waiguan (TE 5) remained within the range of (44±1) °C during both moxibustion methods, with no statistically significant difference (P>0.05). Compared with that before moxibustion, the MBPU of the left Waiguan (TE 5) was increased significantly at 5, 10, 15, and 20 min of both moxibustion methods (P<0.05, P<0.01). Compared with moxibustion for 10, 15 and 20 min, the MBPU of the left Waiguan (TE 5) of moxibustion for 5 min was lower in both moxibustion methods (P<0.01). For both moxibustion methods with the same moxibustion course, the MBPU of the left Waiguan (TE 5) 20 min after intervention was significantly higher than that at 1 min before moxibustion (P<0.001), and there was no significant difference in MBPU between 1 min before moxibustion and 20 min after moxibustion among different groups (P>0.05). Within the same moxibustion method, the MBPU of the left Waiguan (TE 5) 20 min after moxibustion with the intervention of 5 min was lower compared to that of 10, 15, and 20 min of moxibustion (P<0.001), with no significant differences between 10, 15, and 20 min of moxibustion (P>0.05). CONCLUSIONS: When controlling the skin temperature at Waiguan (TE 5) within (44±1) °C, infrared mild moxibustion has similar effects on skin microcirculatory blood perfusion as traditional mild moxibustion with moxa sticks. From a dose-response perspective, microcirculation reached a stable state after 10 min of moxibustion, and moxibustion interventions lasting for more than 10 min shows better therapeutic effects.

Acupuncture Pretreatment Reduces Skeletal Muscle Inflammatory Response in EIMD Rats by Activating cGAS-STING-NF-κB Signaling Pathway.

Acupuncture pretreatment (AP) has a good skeletal muscle protective effect. The present study investigated whether acupuncture pretreatment could improve ultrastructural changes and skeletal muscle inflammation in exercising skeletal muscle injury. Eighty-eight male SD rats were randomly divided into a blank group (C), an exercise group (E), and an acupuncture pretreatment group (AP). Among them, the E and AP groups were divided into five subgroups of 0h, 12h, 24h, 48h, and 72h according to the extraction time after exercise, with 11 groups and eight rats in each group. The study involved simulating skeletal muscle injury caused by intermittent downhill running centrifugal exercise. The researchers used various methods to observe changes in mitochondrial structure and cGAS-STING-NF-κB p65 protein content of classical inflammatory response signaling pathway. These methods included transmission electron microscopy to observe skeletal muscle, Western Blot to detect changes in protein content, and reverse transcription polymerase chain reaction (RT-qPCR method) to detect cytoplasmic mtDNA gene fragment ND1, D-LOOP and cGAS-STING- NF-κB p65 protein RNA. The aim was to investigate the changes in NF-κB p65 protein RNA. Changes in NF-κB p65 protein RNA content and mtDNA gene fragment ND1 and D-LOOP content; changes in serum IL-8 and IFN-ß content were detected by enzyme-linked immunosorbent assay (ELISA); WB, RT-qPCR, ELISA assays aimed to study the skeletal muscle injury and mitochondrial structural damage in group E relationship skeletal muscle tissue level, cytoplasmic mtDNA fragment gene ND1, and D-LOOP content in skeletal muscle tissue of group E. In comparison to group C, the levels of cGAS-STING-NF-κB p65 protein expression and mRNA, and the serum levels of IL-8 and IFN-ß were significantly higher in group E . However, the acupuncture pretreatment group (AP) reduced the extent of damage to skeletal muscle mitochondria and the levels of cytoplasmic mtDNA fragment genes ND1 and D-LOOP. Also, the high expression of cGAS-STING-NF-κB p65 protein, mRNA, and the levels of IL-8 and IFN-ß were inhibited in the AP group. The results indicated that AP ameliorated exercise-induced skeletal muscle injury and reduced skeletal muscle inflammation produced after centrifugal exercise. This was achieved by inhibiting the overexpression of the cGAS-STING-NF-κB signaling pathway.

Analgesic effects of perioperative acupuncture methods: A narrative review.

Postoperative pain occurs immediately after surgery. The most common perioperative analgesic methods are nerve block, patient-controlled intravenous analgesia, and patient-controlled epidural analgesia. However, overuse of opioid analgesics can cause many adverse reactions including excessive sedation, respiratory inhibition, postoperative nausea, and vomiting. In recent years, many clinical trials have shown that perioperative acupuncture has unique advantages in patients. Perioperative acupuncture can relieve intraoperative pain, improve postoperative pain management, reduce postoperative nausea and vomiting, and shorten the length of hospital stay. This study aimed to confirm the analgesic effect of perioperative acupuncture by reviewing studies on the different methods of perioperative acupuncture and their analgesic effects. The cited literature was searched in English and Chinese from PubMed, China National Knowledge Infrastructure, and Wanfang data, using the following keywords: "perioperative pain," "acupuncture," "electroacupuncture," and "perioperative analgesia." Studies published from 2005 to 2023 were included. All retrieved papers were read in detail. Perioperative acupuncture has benefits in reducing postoperative pain and opioid need. Although analgesic drugs are still the primary means of postoperative pain control, acupuncture provides a safe analgesic supplement or alternative. This review aimed to assist practitioners in choosing appropriate perioperative acupuncture methods by summarizing the recent literature on the role of different acupuncture approaches for perioperative pain management.

[Effects of Modified Distiller's Lees Biochar on Nutrients and Enzyme Activities in Purple Soil].

In order to investigate the effects of distiller's lees biochar and different modified distiller's lees biochars on soil properties, pot experiments were conducted to study the effects of different soil amendments (CK:no amendment, JZ:distiller's lees biochar, TiO2/JZ:Nano-TiO2 supported by distiller's lees biochar, and Fe/TiO2/JZ:titanium dioxide supported by iron-modified distiller's lees biochar) and the application rates of different amendments (1%, 3%, and 5%) on the characteristics of soil nutrients and enzyme activities under irrigation-drought rotation. The results showed the following:①the modified distiller's lees biochar significantly increased soil pH and CEC (P<0.05). At the 5% Fe-TiO2/JZ addition level, the soil pH reached 7.95 during the rice season, an increase of 2.3 units compared with that in the CK treatment; the CEC reached 12.06 cmol·kg-1, increasing by 21.38%; the soil pH reached 5.99 during the cabbage season and increased by 1.5 units compared with that in the CK treatment; and CEC reached 8.91 cmol·kg-1 at 3% Fe-TiO2/JZ addition and increased by 13.11%. ②At the same time, the contents of soil total nitrogen and available phosphorus were significantly increased (P<0.05). Compared with that in the CK treatment, the soil total nitrogen of 5% JZ, 5% TiO2/JZ, and 5% Fe-TiO2/JZ increased by 20.56%, 85.04%, and 59.61% in the rice season and 12.39%, 22.68%, and 23.70% in the cabbage season, respectively. In the rice season, the increase in soil available P under 5% Fe-TiO2/JZ was the highest, reaching 10.49 mg·kg-1, which was 1.64 times that under CK treatment. In the cabbage season, the soil available phosphorus (P) reached 90.15 mg·kg-1 under 5% TiO2/JZ addition, which increased by 93.38% compared with that in the CK treatment. ③Modified distiller's lees biochar increased catalase and urease activities and decreased alkali-hydrolytic nitrogen content and acid phosphatase activity. At the 3% addition level, catalase activity increased by 12.19%, 48.17%, and 37.30% in the rice season and 5.95%, 8.34%, and 17.42% in the cabbage season, respectively. In the rice season, the soil urease activity reached the maximum under 5% Fe-TiO2/JZ addition, which was increased by 40.90% compared with that in the CK treatment. In the cabbage season, the soil urease activity reached the maximum under 5% TiO2/JZ addition, which was increased by 58.53% compared with that in the CK treatment. The activity of acid phosphatase decreased by 5.39%-24.66% in the rice season and by 54.46%-61.40% in the cabbage season. Distiller's lees biochar and modified distiller's lees biochar could effectively increase soil pH and soil nutrient content, thus affecting soil enzyme activities. The application of iron modified-titanium dioxide-loaded distiller's lees biochar of 3% to 5% in acidic purple soil is more suitable.

[Current status and trend of acupuncture-moxibustion for myofascial pain syndrome: a visual analysis of knowledge graph based on CiteSpace and VOSviewer].

Bibliometric and scientific knowledge graph methods were used to analyze the research status and hot spots of acupuncture-moxibustion in treatment of myofascial pain syndrome (MPS) and explore its development trend. The articles of both Chinese and English versions relevant to MPS treated by acupuncture-moxibustion were searched in CNKI, VIP, Wanfang, SinoMed and WOS from the database inception to March 20, 2023. Using Excel2016, CiteSpace6.2.R2 and VOSviewer1.6.18, the visual analysis was conducted by means of the cooperative network, keyword co-occurrence, keyword timeline, keyword emergence, etc. From Chinese databases and WOS database, 910 Chinese articles and 300 English articles were included, respectively. The annual publication volume showed an overall rising trend. Literature output of English articles was concentrated in Spain, China, and the United States, of which, there was less cross-regional cooperation. In the keyword analysis, regarding acupuncture-moxibustion therapy, Chinese articles focused on "acupuncture", "electroacupuncture" and "acupotomy"; while, "dry needling" and "injection" were dominated for English one. Clinical study was the current hot spot in Chinese databases, in comparison, the randomized controlled double-blind clinical trial was predominant in WOS. Both Chinese and English articles were limited in the report of mechanism research. The cooperation among research teams should be strengthened to conduct comparative research, dose-effect research and effect mechanism research with different methods of acupuncture-moxibustion involved so that the evidences can be provided for deeper exploration.

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

Melatonin ameliorates histone modification disorders in mammalian aged oocytes by neutralizing the alkylation of HDAC1.

Aging-associated histone modification changes in oocytes have been sporadically reported, but the underlying mechanisms remain elusive. Here, we systematically characterize multiple histone modifications in oocytes during aging. We find that maternal and postovulatory aging markedly alter the status of histone modifications, specifically H4K12ac and H3K4me3, in both mouse and porcine oocytes. Meanwhile, we identify a substantial reduction in HDAC1 (histone deacetylase 1) protein in aged oocytes, which contributes to the changes in H4K12ac and H3K4me3. Moreover, by employing methylglyoxal (MG) and site-directed mutagenesis, we demonstrate that the elevated reactive carbonyl species (RCS) level induces HDAC1 degradation, likely through attacking the cysteine residues, thereby influences histone modification state. Importantly, supplementation of melatonin not only prevents the loss of HDAC1 protein, but also partially corrects the H4K12ac and H3K4me3 status in aged oocytes. To sum up, this study established the link between redox disequilibrium and histone modification alterations during mammalian oocyte aging.

[Development and application of visual analysis teaching software for acupoint compatibility laws].

A user-friendly teaching software for visual analysis of acupoint compatibility laws has been developed based on the principles of partial order mathematics. This software is designed to provide auxiliary teaching of structured organization and visualization of law knowledge of compatibility data of acupuncture and moxibustion prescriptions from ancient texts, textbooks, and clinical case records. The software is installed as a plugin in the Microsoft Office Excel, allowing the generation of visually appealing graphs and associated rules that align with the cognitive patterns of teachers and students majoring in acupuncture and moxibustion. Its aim is to facilitate the discovery and analysis of underlying patterns and structured knowledge embedded in acupoint compatibility data, thus contributing to the enhancement of teaching effectiveness in acupoint compatibility.

Emerging 2D pnictogens: a novel multifunctional photonic nanoplatform for cutting-edge precision treatment.

The elements of the pnictogen group, known as the 15th (VA) family in the periodic table, including phosphorus (P), arsenic (As), antimony (Sb) and bismuth (Bi), have been widely used by alchemists to treat various diseases since ancient times and hold a pivotal position in the history of medicine, owing to their diverse pharmacological activities. Recently, with the development of modern nanotechnology, pnictogen group elements appear in a more innovative form, namely two-dimensional (2D) pnictogens (i.e. phosphorene, arsenene, and bismuthene) with a unique layered crystal structure and extraordinary optoelectronic characteristics, which endow them with significant superiority as a novel multifunctional photonic nanoplatform for cutting-edge precision treatment of various diseases. The puckered layer structure with ultralarge surface area make them ideal drug and gene delivery vectors that can avoid degradation and reduce target effects. The anisotropic morphology allows their easier internalization by cells and may improve gene transfection efficiency. Tunable optoelectronic characteristics endow them with excellent phototherapy performance as well as the ability to act as an optical switch to initiate subsequent therapeutic events. This review provides a brief overview of the properties, preparation and surface modifications of 2D pnictogens, and then focuses on its applications in cutting-edge precision treatment as a novel multifunctional photonic nanoplatform, such as phototherapy, photonic medicine, photo-adjuvant immunotherapy and photo-assisted gene therapy. Finally, the challenges and future development trends for 2D pnictogens are provided. With a focus on 2D pnictogen-based multifunctional photonic nanoplatforms, this review may also provide profound insights for the next generation innovative precision therapy.

[Clinical observation on electroacupuncture at "four points of sacral region" on moderate to severe stress urinary incontinence after radical prostatectomy].

OBJECTIVE: To compare the clinical therapeutic effect between electroacupuncture at "four points of sacral region" and transurethral Erbium laser in treatment of moderate to severe stress urinary incontinence after radical prostatectomy. METHODS: A total of 68 patients of moderate to severe stress urinary incontinence after radical prostatectomy were divided into an electroacupuncture group (34 cases) and an Erbium laser group (34 cases, 3 cases dropped off) according to the settings. In the electroacupuncture group, electroacupuncture was applied at "four points of sacral region", i.e. points of 0.5 cun beside bilateral sacrococcygeal joints and bilateral Huiyang (BL 35), with continuous wave, 2 Hz in frequency, 60 min each time, once every other day, 3 times a week, 12 times as one course of treatment. In the Erbium laser group, transurethral Erbium laser technology was given, once every 4 weeks as one course of treatment. Both groups were treated for 5 courses. The scores of the International Consultation on Incontinence questionnaire-short form (ICI-Q-SF) and the incontinence quality of life questionnaire (I-QOL) were observed before treatment, after each course of treatment and in follow-up after 1 and 2 months of treatment completion, respectively, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: Compared with those before treatment, the ICI-Q-SF scores were decreased while the I-QOL scores were increased after 5 courses of treatment and in follow-up after 1, 2 months of treatment completion in the two groups (P<0.01). The ICI-Q-SF score in follow-up after 2 months of treatment completion were higher than that after 5 courses of treatment in the Erbium laser group (P<0.05). After 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the ICI-Q-SF scores in the electroacupuncture group were lower than those in the Erbium laser group (P<0.05, P<0.01); after 2, 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the I-QOL scores in the electroacupuncture group were higher than those in the Erbium laser group (P<0.01). The change ranges of ICI-Q-SF score and I-QOL score between before treatment and after each course of treatment in the electroacupuncture group were lager than those in the Erbium laser group (P<0.01, P<0.05). The total effective rate was 61.8% (21/34) in the electroacupuncture group, which was superior to 19.4 (6/31) in the Erbium laser group (P<0.01). CONCLUSION: Both electroacupuncture at "four points of sacral region" and transurethral Erbium laser can improve the clinical symptoms and the quality of life in patients of moderate to severe stress urinary incontinence after radical prostatectomy. The short-term efficacy and long-term efficacy of electroacupuncture are superior to the Erbium laser technology.

Syk-dependent alternative homologous recombination activation promotes cancer resistance to DNA targeted therapy.

Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase known to regulate immune cell function, cell adhesion, and vascular development. Here, we report that Syk can be expressed in high grade serous ovarian cancer and triple negative breast cancers and promotes DNA double strand break resection, homologous recombination (HR) and therapeutic resistance. We found that Syk is activated by ATM following DNA damage and is recruited to DNA double strand breaks by NBS1. Once at the break site, Syk phosphorylates CtIP, a key mediator of resection and HR, at Thr-847 to promote repair activity, specifically in Syk expressing cancer cells. Syk inhibition or genetic deletion abolished CtIP Thr-847 phosphorylation and overcame the resistant phenotype. Collectively, our findings suggest that Syk drives therapeutic resistance by promoting DNA resection and HR through a novel ATM-Syk-CtIP pathway, and that Syk is a new tumor-specific target to sensitize Syk-expressing tumors to PARPi and other DNA targeted therapy.

[Relationship between pyroptosis and cardiovascular diseases and traditional Chinese medicine prevention and treatment research].

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.