Adjustable ultraviolet and white light dual emission phosphor Y2Sr(Ga1-yAly)4SiO12:xPr3+ for health lighting.

Mid-ultraviolet light (290-320 nm) can promote human vitamin D synthesis, which helps in the prevention and treatment of rickets and cartilage disease. For people who lack sufficient ultraviolet radiation all year round, it is significant to supplement the ultraviolet component in daily lighting sources. However, there are few luminous materials showing a combination of mid-ultraviolet light and white light emission on the market. Here, we designed a new material, Y2Sr(Ga1-yAly)4SiO12:xPr3+ (YSGAS:xPr3+), which achieves dual emission of 320 nm ultraviolet and white light from a single substrate with a single doped phosphor. Without Al3+ ions, the emission intensity of the Y2SrGa4SiO12:xPr3+ phosphor shows a contribution-dependent relationship, and concentration quenching due to exchange interaction. The crystal field environment was regulated by partially replacing Ga3+ ions with Al3+ ions. After introducing Al3+, YSGAS:xPr3+ phosphors exhibit dual ultraviolet emission (320 nm) and visible light emission. The emission color of YSGAS:xPr3+ can be adjusted by changing the Al3+ concentration, and Y2Sr(Ga0.6Al0.4)4SiO12:1%Pr3+ emits both ultraviolet light and white light. The LED device prepared by using the YSGAS:Pr3+ phosphor and chips shows a color temperature of 4858 K and appropriate CIE coordinates of (0.3474, 0.3390), indicating wide application prospects in the field of "health lighting" for particular populations.

Tetramethylpyrazine alleviates hypoxia-induced proliferation, migration, and inflammatory response of fibroblast-like synoviocytes via inhibiting the HIF-1α- circCDC42BPB pathway.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which might trigger cartilage, bone damage, and disability. Recent studies have suggested that Tetramethylpyrazine (TMP), an alkaloid monomer isolated from the rhizome of the traditional herbal medicine Ligusticum wallichii Franch, exerts a broad spectrum of pharmacological properties, containing anti-inflammatory. This study aimed to analyze the role and underlying mechanism of TMP in RA. METHODS: Under Hypoxia condition, RA-Fibroblast-like synoviocyte (FLS) were treated with TMP at different doses. Cell viability, proliferation, cell cycle progression, and migration were detected using Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry assay, wound healing assay, and transwell assay. Cyclin D1, Proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase-2 (MMP2), MMP9, and hypoxia-inducible factor-1α (HIF-1α) protein levels were measured using western blot assay. Interleukin-6 (IL-6) and IL-8 were evaluated using ELISA. Circular RNA (circRNA) hsa_circ_0005178 (circCDC42BPB), CDC42BPB, and HIF-1α expression were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Binding between HIF-1α and CDC42BPB promoter was predicted by JASPAR and verified using dual-luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. RESULTS: TMP might hinder FLS proliferation, cycle progression, migration, and inflammatory response under hypoxic conditions. CircCDC42BPB expression was increased in RA patients and RA-FLSs treated with hypoxia, while its level was obviously reduced in RA-FLSs treated with hypoxia and TMP. TMP might abolish hypoxia-induced circCDC42BPB expression. Upregulation of circCDC42BPB might partially overturn the repression of TMP on hypoxia-caused RA-FLS damage. TMP might regulate circCDC42BPB level via HIF-1α in RA-FLSs under hypoxic conditions. CONCLUSION: TMP might block RA-FLS injury partly via regulating the HIF-1α- circCDC42BPB pathway, providing a promising therapeutic target for RA.

HIGHLIGHTS: • TMP suppressed hypoxia-induced RA-FLS growth and inflammatory response.• TMP might repress circCDC42BPB expression in RA-FLSs under hypoxic conditions.• TMP might inhibit HIF-1α-induced circCDC42BPB transcription under hypoxic conditions.

Comparative study on curative effect and recurrence rate of chronic scapulohumeral periarthritis treated with different acupuncture techniques. / ä¸åŒé’ˆæ³•æ²»ç–—æ ¢æ€§è‚©å ³èŠ‚å‘¨å›´ç‚Žçš„ç–—æ•ˆåŠå¤å‘çŽ‡çš„å¯¹æ¯”ç ”ç©¶.

OBJECTIVES: To observe the effects of the local stimulation with 3 acupuncture techniques, i.e. Canggui Tanxue (needle insertion method like dark tortoise detecting point) technique, electroacupuncture (EA) and warm needling (WN) with filiform needles on shoulder pain, shoulder joint function, quality of life, inflammatory indicators and recurrence rate in the patients with chronic scapulohumeral periarthritis (CSP), so as to explore the optimal needling method of acupuncture for the predominant symptoms of CSP during the attack stage in the patients. METHODS: A total of 108 patients with CSP were randomly divided into a manual acupuncture (MA) group (36 cases, one case dropped off), a WN group (36 cases, 3 cases dropped off) and an EA group (36 cases, 1 case dropped off). In the three groups, Jianqian (EX-UE12), Jianyu (LI15), Jianzhen (SI9), Ashi (Extra) and Yanglingquan (GB34) on the affected side were selected. Canggui Tanxue needling technique, WN technique and EA were delivered in the MA group, the WN group and the EA group, respectively, 30 min each time, 3 times weekly for 4 weeks. The Neer test scores were compared；the visual analogue scale (VAS) was used to assess the degree of shoulder joint pain；the daily life activity abilities was evaluated using the activities of daily living (ADL) scale；the serum prostaglandin E2 (PGE2) content was measured using ELISA before and after treatment. The effectiveness rate and recurrence rate were calculated, and the occurrences of adverse reactions were recorded. RESULTS: Compared with the scores before treatment, the scores of pain, joint function, and range of motion as well as the total score of Neer test were all increased after treatment in the three groups (P<0.05)；the VAS score, ADL score and the content of serum PGE2 were decreased (P<0.05). After treatment, the pain score of Neer test in the EA group and the WN group were higher than those of the MA group (P<0.05), the joint function score of Neer test in the MA group and the WN group were higher than that of the EA group (P<0.05), and the range of motion score of Neer test in the MA group was higher when compared with the EA and WN groups (P<0.05). There was no statistical difference in the total score of Neer score among the three groups. VAS score in the EA group was lower than that of either the WN group or the MA group (P<0.05). ADL score in the MA group was lower compared with that of the WN group (P<0.05). PGE2 levels in both the WN group and the MA group were lower than that of the EA group (P<0.05). The total effective rate was 85.71% (30/35) in the MA group, 91.43% (32/35) in the EA group and 90.91% (30/33) in the WN group, there was no statistical differences among the three groups. At the end of the 6-month follow-up visit after treatment, there was no significant difference in the recurrence rate among three groups. No serious adverse reaction was found. CONCLUSIONS: In the treatment of CSP, the short-term effect is equivalent among EA, WN and MA. But, the analgesic effect is the best in the EA group, the treatment for anti-inflammation is the most effective in the MA and WN groups, and the needling technique of Canggui Tanxue in the MA group obtains the most favorable effect of releasing adhesion and recovering the range of motion in the shoulder joint.

Interactions of rhizosphere microbiota-environmental factors-pharmacological active ingredients of Eucommia ulmoides.

MAIN CONCLUSION: The composition, diversity and co-occurrence patterns of the rhizosphere microbiota of E. ulmoides were significantly influenced by environmental factors, and which were potentially associated with the contents of pharmacological active ingredients. Eucommia ulmoides is an important perennial medicinal plant. However, little is known about the interactions among microbiota, environmental factors (EFs), and pharmacological active ingredients (PAIs) of E. ulmoides. Herein, we analyzed the interactions among rhizosphere microbiota-EFs-PAIs of E. ulmoides by amplicon sequencing and multi-analytical approach. Our results revealed variations in the dominant genera, diversity, and co-occurrence networks of the rhizosphere microbiota of E. ulmoides across different geographical locations. Notably, available nitrogen exerted the strongest influence on fungal dominant genera, while pH significantly impacted bacterial dominant genera. Rainfall and relative humidity exhibited pronounced effects on the α-diversity of fungal groups, whereas available phosphorus influenced the number of nodes in fungal co-occurrence networks. Altitude and total phosphorus had substantial effects on the average degree and nodes in bacterial co-occurrence networks. Furthermore, the dominant genera, diversity and co-occurrence network of rhizosphere microbiota of E. ulmoides were significantly correlated with the content of PAIs. Specifically, the abundance of rhizosphere dominant genera Filobasidium, Hannaella and Nitrospira were significantly correlated with the content of pinoresinol diglucoside (PD). Similarly, the abundance of Vishniacozyma and Bradyrhizobium correlated significantly with the content of geniposidic acid (GC), while the abundance of Gemmatimonas was significantly correlated with the content of aucubin. Moreover, the bacterial co-occurrence network parameters including average degree, density, and edge, were significantly correlated with the content of GC and aucubin. The α-diversity index Chao1 also displayed a significant correlation with the content of PD. These findings contribute to a more comprehensive understanding of the interactions between medicinal plants and microbes.

Brain microvascular endothelial cell-derived exosomes transmitting circ_0000495 promote microglial M1-polarization and endothelial cell injury under hypoxia condition.

Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs-derived exosomes in microglia polarization after stroke remains unknown. We isolated exosomes (Exos) from oxygen glucose deprivation (OGD)-exposed HBMVECs, before added them into microglia. Microglia polarization markers were tested using RT-qPCR or flow cytometry. Inflammatory cytokines were measured with ELISA. Endothelial cell damage was assessed by cell viability, apoptosis, apoptosis-related proteins, oxidative stress, and angiogenic activity using CCK-8, flow cytometry, western blot, ELISA, and endothelial tube formation assay, respectively. We also established middle cerebral artery occlusion (MCAO) mice model to examine the function of circ_0000495 on stroke in vivo. Our study found that HBMVECs-Exos reduced M2 markers (IL-10, CD163, and CD206), increased M1 markers (TNF-α, IL-1ß, and IL-12), CD86-positive cells, and inflammatory cytokines (TNF-α and IL-1ß), indicating the promotion of microglial M1-polarization. Microglial M1-polarization induced by HBMVECs-Exos reduced viability and promoted apoptosis and oxidative stress, revealing the aggravation of endothelial cell damage. However, circ_0000495 silencing inhibited HBMVECs-Exos-induced alterations. Mechanistically, circ_0000495 adsorbed miR-579-3p to upregulate toll-like receptor 4 (TLR4) in microglia; miR-579-3p suppressed HBMVECs-Exos-induced alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated circ_0000495 in HBMVECs. Importantly, circ_0000495 aggravated ischemic brain injury in vivo via activating TLR4/nuclear factor-κB (NF-κB) pathway. Collectively, OGD-treated HBMVECs-Exos transmitted circ_0000495 to regulate miR-579-3p/TLR4/NF-κB axis in microglia, thereby facilitating microglial M1-polarization and endothelial cell damage.

Sophora tonkinensis and active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency in myocardial ischemia mice through regulating the vesicle-mediated transport pathway.

Ancient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1ß, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI.

Phosphate deficiency responsive TaSPX3 is involved in the regulation of shoot phosphorus in Arabidopsis plants.

SPX (SYG/PHO81/XPR1) domain genes have been reported to play vital roles in the Phosphorus (Pi) signaling network in Arabidopsis thaliana and rice. However, the functions of SPX proteins in wheat remain largely unknown. In this study, the full-length cDNA sequence of the TaSPX3 gene was cloned from the common wheat variety Zhengmai9023. The expression of TaSPX3 was up-regulated in eight different genotypes of wheat under low phosphorus (LP) stress, indicating that TaSPX3 responds to Pi limitation in multiple wheat genotypes. The transcription level of TaSPX3 was also detected in the absence of seven different elements, showing certain specificity for Pi deficiency in wheat. Over expressing TaSPX3 in Arabidopsis can alleviate Pi deficiency symptoms at the seedling stage and promote the growth of plant, and advance the flowering period at the adult stage. The expression of 7 genes associated with the Pi starvation signal pathways was analyzed using qRT-PCR. The results showed that TaSPX3, along with AtSPX1, AtRNS1, AtIPS1, AtPAP2, AtPAP17 and AtAT4, were all induced by Pi deficiency. This study reveals that the TaSPX3 gene in wheat is involved in the response to phosphorus stress and may affect shoot phosphorus levels through AT4 or PAPs-related pathways. Overall, our study provides new insights into the regulation of plant response under LP conditions and the molecular mechanism underlying the role of the wheat SPX gene in coping with LP stress.

Chinese counseling trainees' trait and state mindfulness and client symptom outcome: A longitudinal examination with multilevel and random-intercept cross-lagged panel models.

This study aimed to explore how Chinese counseling trainees' trait and state mindfulness predicted their clients' symptom level over the course of therapy. A data set consisting of 6,888 sessions from 1,216 clients and their 211 master's level beginning therapist trainees in China was used, which included a measure of trainees' trait mindfulness at the beginning of their practicum and their state mindfulness and client-rated symptom distress level at the beginning of each of their therapy sessions. Multilevel modeling and random-intercept cross-lagged panel model results suggested that (a) at the trainee level, a trainee's trait mindfulness did not predict their average client symptom improvement over practicum; (b) at the session-to-session level, higher trainee state mindfulness before one session significantly predicted lower client distress before the next session, and higher client distress before one session did not predict trainee state mindfulness before the subsequent session. Findings suggested that it was the trainees' session-to-session state mindfulness, instead of their general trait mindfulness, that temporally led to greater client symptom reduction. Implications for clinical training were discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preventive effects of caffeine on nicotine plus high-fat diet-induced hepatic steatosis and gain weight: a possible explanation for why obese smokers with high coffee consumption tend to be leaner.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder, affecting approximately 25 % of the population. Coffee-drinking obese smokers exhibit lower body weights and decreased NAFLD rates, but the reasons behind this remain unclear. Additionally, the effect of nicotine, the main component of tobacco, on the development of NAFLD is still controversial. Our study aimed to explore the possible reasons that drinking coffee could alleviate NAFLD and gain weight and identify the real role of nicotine in NAFLD of obese smokers. A NAFLD model in mice was induced by administering nicotine and a high-fat diet (HFD). We recorded changes in body weight and daily food intake, measured the weights of the liver and visceral fat, and observed liver and adipose tissue histopathology. Lipid levels, liver function, liver malondialdehyde (MDA), superoxide dismutase (SOD), serum inflammatory cytokine levels and the expression of hepatic genes involved in lipid metabolism were determined. Our results demonstrated that nicotine exacerbated the development of NAFLD and caffeine had a hepatoprotective effect on NAFLD. The administration of caffeine could ameliorate nicotine-plus-HFD-induced NAFLD by reducing lipid accumulation, regulating hepatic lipid metabolism, alleviating oxidative stress, attenuating inflammatory response and restoring hepatic functions. These results might explain why obese smokers with high coffee consumption exhibit the lower incidence rate of NAFLD and tend to be leaner. It is essential to emphasise that the detrimental impact of smoking on health is multifaceted. Smoking cessation remains the sole practical and effective strategy for averting the tobacco-related complications and reducing the risk of mortality.

Xinfeng capsule inhibits lncRNA NONHSAT227927.1/TRAF2 to alleviate NF-κB-p65-induced immuno-inflammation in ankylosing spondylitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ankylosing spondylitis (AS) is a chronic rheumatic disease known for its insidious and refractory symptoms, primarily associated with immuno-inflammation in its early stages, that affects the self-perception of patients (SPP). The exploration of long noncoding RNA (lncRNA) in immuno-inflammation of AS has garnered considerable interest. Additionally, the effectiveness of traditional Chinese medicine Xinfeng Capsule (XFC) in mitigating immuno-inflammation in AS has also been observed. However, the specific mechanisms still need to be characterized. AIM OF THE STUDY: This study elucidated the mechanism of the lncRNA NONHSAT227927.1/TRAF2/NF-κB axis in the immuno-inflammation of AS and XFC in AS treatment. METHODS: LncRNA NONHSAT227927.1 and mRNA expression were assessed utilizing real-time fluorescence quantitative PCR. Protein level was determined using Western blot, and cytokine expression was measured using ELISA. Furthermore, mass spectrometry was used to analyze the binding proteins of lncRNA and rescue experiments were conducted to validate the findings. Inconsistencies in clinical baseline data were addressed using propensity score matching. The association between the XFC effect and indicator changes was evaluated using the Apriori algorithm. RESULTS: The study revealed a substantial elevation in the expression of lncRNA NONHSAT227927.1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) in AS-peripheral blood mononuclear cells. Its expression was also notably reduced after XFC treatment. In addition to this, there was a positive correlation between lncRNA NONHSAT227927.1 and TRAF2 with clinical immuno-inflammatory indicators. On the other hand, they showed a negative association with the SPP indicators. In vitro experiments have demonstrated that lncRNA NONHSAT227927.1 activated the nuclear factor (NF)-κB-p65 pathway by promoting TRAF2 expression. This activation resulted in enhanced IL-6 and TNF-α levels and reduced IL-10 and IL-4 levels. Conversely, XFC decreased the expression of lncRNA NONHSAT227927.1 and TRAF2, inhibiting the stimulation of the NF-κB-p65 cascade and restoring balance to the cytokines. The association rule analysis results indicated a strong association between XFC and decreased levels of C-reactive protein, erythrocyte sedimentation rate, and immunoglobulin A. Furthermore, XFC was strongly associated with improved SPP indicators, including general health, vitality, mental health, and role-emotional. CONCLUSIONS: LncRNA NONHSAT227927.1 plays a pro-inflammatory role in AS. XFC treatment may reverse lncRNA NONHSAT227927.1 to suppress TRAF2-mediated NF-κB-p65 activation, which in turn suppresses immuno-inflammation and improves SPP, thereby making XFC a promising candidate for therapeutic applications in AS management.

The molecular cytoarchitecture of the adult mouse brain.

The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2-a recently developed spatial transcriptomics method with near-cellular resolution-across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource ( www.BrainCellData.org ), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.

Du-Moxibustion in a Mouse Model of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a progressively worsening and disabling form of arthritis that primarily affects the axial skeleton. This disease mainly involves the spine and the sacroiliac joint. Fusion of the spine and the sacroiliac joint may occur in the later stage of the disease, resulting in spinal stiffness and kyphosis, as well as difficulty in walking, which seriously affects the quality of work and daily living activities and imposes a heavy burden on the patient, the family, and society. Increasing attention has been paid to non-pharmacotherapy as an alternative therapy for AS. Moxibustion is an ancient therapeutic technique used in Traditional Chinese Medicine (TCM). Du-moxibustion therapy, a unique and innovative external treatment developed on the basis of ordinary moxibustion, has a definite therapeutic effect on AS. Du-moxibustion skillfully combines the compatible techniques of TCM to integrate meridians, acupoints, Chinese herbal medicine, and moxibustion. This paper describes the operation procedures and precautions to be taken during Du-moxibustion in experimental mice in detail to provide an experimental basis for the study of the mechanism of Du-moxibustion in the treatment of AS.

[Evaluation of low intensity Nd: YAG laser and traditional drugs in the treatment of myofascial pain].

PURPOSE: To evaluate the efficacy of low intensity Nd: YAG laser and traditional drugs in the treatment of myofascial pain (MP). METHODS: Eighty patients with MP were divided into laser group(n=40) and traditional medicine group(n=40) according to the principle of randomization and double-blindness. The patients in the laser group were treated with low intensity Nd :YAG laser(1 064 nm, 8 J/cm2, 250 mW) , with an interval of 48 h between the two laser treatments. The whole course of treatment was 10 times. Patients in the traditional medicine group uesd celecoxib capsules, 1 capsulet each time(0.2 g), twice a day for 2 weeks. Before and after each treatment, mouth opening, protrusion excursion, lateral movement of the affected side and lateral movement of the contralateral side were measured, and pain visual analogue scores (VAS) were measured and recorded. The data were statistically analyzed with SPSS 22.0 software package. RESULTS: Patients in laser group had significantly improved mandibular function and movement status(P＜0.05) and pain symptoms(P＜0.05); patients in traditional medicine group had the same significant improvement on mandibular functional movement status(P＜0.05) and pain symptoms (P＜0.05). The total effective rate of the two groups had no significant difference(P＞0.05). The VAS score of patients in laser group was lower than that of traditional medicine group, but the difference was not significant(P＞0.05). CONCLUSIONS: Low intensity Nd: YAG laser and traditional medicine can effectively relieve the symptoms of myofascial pain and improve mandibular function and movement. Laser treatment has the advantages of short course of treatment, high efficiency, no pain and fewer side effects, which is worthy of clinical application.

Optimized electroacupuncture treatment for female stress urinary incontinence: study protocol for a multi-center randomized controlled trial.

Background: Stress urinary incontinence (SUI) is a common condition that can severely affect women's life quality. Electroacupuncture (EA) has been proved to be an optional treatment for SUI, but the tolerance of EA becomes a factor affecting efficiency, which should not be ignored and needs to be solved urgently. The purpose of this study is to find out whether the use of alternating acupoints combination can solve this problem or not and provide an optimization of EA treatment for female SUI. Methods: This multi-center randomized controlled trial will enroll 360 patients with SUI. They will be randomly assigned to one of the three groups-sacral acupoints group (sacral group), abdominal acupoints group (abdominal group), or alternating acupoints group (alternating group)-at a 1:1:1 ratio. The patients will receive 18 sessions of EA treatment and will be followed up for 48 weeks after the treatment. The primary outcome measure of the study is the change of urine leakage at week 6. The secondary outcomes include the incontinence episode frequency (IEF), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), severity of SUI, patient self-evaluation of therapeutic effects, weekly usage of urine pads, ultrasonography of pelvic floor, specialty therapies for SUI, evaluation of discomfort during EA treatment, patient acceptability evaluation and adverse events related to intervention. Discussion: This trial is specifically designed to offer an optimized EA treatment for female SUI, aiming to enhance their quality of life.Clinical trial registration: ClinicalTrials.gov, identifier ID:NCT05635669.

Lycorine inhibits pancreatic cancer cell growth and neovascularization by inducing Notch1 degradation and downregulating key vasculogenic genes.

Pancreatic cancer is highly metastatic and lethal with an increasing incidence globally and a 5-year survival rate of only 8%. One of the factors contributing to the high mortality is the lack of effective drugs in the clinical setting. We speculated that effective compounds against pancreatic cancer exist in natural herbs and explored active small molecules among traditional Chinese medicinal herbs. The small molecule lycorine (MW: 323.77) derived from the herb Lycoris radiata inhibited pancreatic cancer cell growth with an IC50 value of 1 µM in a concentration-dependent manner. Lycorine markedly reduced pancreatic cancer cell viability, migration, invasion, neovascularization, and gemcitabine resistance. Additionally, lycorine effectively suppressed tumor growth in mouse xenograft models without obvious toxicity. Pharmacological studies revealed that the levels and half-life of Notch1 oncoprotein in the pancreatic cancer cells Panc-1 and Patu8988 were notably reduced. Moreover, the expression of the key vasculogenic genes Semaphorin 4D (Sema4D) and angiopoietin-2 (Ang-2) were also significantly inhibited by lycorine. Mechanistically, lycorine strongly triggered the degradation of Notch1 oncoprotein through the ubiquitin-proteasome system. In conclusion, lycorine effectively inhibits pancreatic cancer cell growth, migration, invasion, neovascularization, and gemcitabine resistance by inducing degradation of Notch1 oncoprotein and downregulating the key vasculogenic genes Sema4D and Ang-2. Our findings provide a new therapeutic candidate and treatment strategy against pancreatic cancer.

Luteolin inhibits A549 cells proliferation and migration by down-regulating androgen receptors.

BACKGROUND: Yi Fei Qing Hua Granules (YQG) is a traditional Chinese herbal medicine with the effects of inhibiting the proliferation of lung cancer cells. Luteolin is one of the active compounds of YQG. Luteolin is a common flavonoid extracted from natural herbs and it can promote cancer cells apoptosis has been reported. However, the underlying molecular mechanism and effects of luteolin on human lung cancer needs to be validated. METHODS: Molecular docking, network pharmacology methods and quantitative structure-activity relationship (QSAR) model were used to identify the active components of YQG and their possible mechanisms of action. Western blot analysis was used to measure AR expression in A549 cells. Cell migration assays were used to detect A549 cells proliferation transfected by AR plasmid and AR mutation plasmid, respectively. RESULTS: TCMSP search results revealed that there are 182 active compounds in YQG, which correspond to 232 target genes. Sixty-one genes were overlapping genes in the 2 datasets of TCMSP and GeneCards. Through bioinformatics tagging of these overlapping genes, a total of 1,951 GO functional tagging analysis and 133 KEGG pathways were obtained. Through molecular docking technology and QSAR model verification, the multi-target active compound luteolin was screened out as one of the active components of YQG for in vitro verification. Androgen receptor (AR) was the hub protein with the highest docking score of luteolin. Western blot showed that luteolin could inhibit AR protein expression in lung cancer cell line A549. After the phosphorylation site of AR protein 877 was inactivated, the ability of luteolin to inhibit the proliferation of lung cancer cells was weakened. Luteolin significantly inhibited the growth of A549 xenogeneic tumors at day 25 and 28 and inhibited the expression of AR. CONCLUSION: In this study, we have explored luteolin as one of the active components of YQG, and may inhibit the proliferation and migration of A549 cells by decreasing the expression of AR and the regulation of phosphorylation at AR-binding sites.

Buyang Huanwu Decoction promotes the neurological recovery of traumatic spinal cord injury via inhibiting apoptosis, inflammation, and oxidative stress.

BACKGROUND: The incidence rate of spinal cord injury (SCI) is increasing, and the mortality or disability rate caused by SCI remains high in the world. Buyang Huanwu Decoction (BYHWD) is a kind of Traditional Chinese medicine, and it is believed to be effective in several kinds of nervous system diseases. Whether BYHWD could improve SCI and the potential function mechanism remain unclear. METHODS: SCI animal model was established by damaging T10 spinal cord. Animals experiments included five groups as follows: Sham, SCI, SCI+BYHWD, SCI+mesenchymal stromal cells (MSCs), and SCI+BYHWD+MSCs. H2 O2 -treated cells (100 µM, 6 h) were used to simulate SCI damage in vitro, which included five groups as follows: control, H2 O2 , H2 O2 +BYHWD, H2 O2 +MSCs, and H2 O2 +BYHWD+MSCs. The behavioral function was evaluated with Tarlov and inclined plated test score. Western blot analysis and immunohistochemical staining were used to detect protein expression. The levels of superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 in serum were measured with commercial enzyme-linked immunosorbent assay kits. terminal deoxynucleotidyl transferase dUTP nick end labeling staining and flow cytometry were performed to measure apoptosis in vivo and in vitro levels. Gene expression profiling analysis was performed to analyze differential expression genes. RESULTS: BYHWD suppressed apoptosis and accelerating cell proliferation after SCI. Recovery of neurofunction, inhibition of inflammatory response, and oxidative condition were achieved by BYHWD and MSCs. The expression levels of gp130/Janus kinase/signal transducers and activator of transcription (JAK/STAT) were suppressed by BYHWD and MSCs, both in vivo and in vitro. BYHWD and MSCs markedly promoted cells viability and inhibited apoptosis. Greater gene expression difference was observed between group control and H2 O2 through gene expression profiling analysis. The recovery effects of traumatic SCI by BYHWD were similar to MSCs, and synergies effects were observed in several items. CONCLUSION: BYHWD could increase Tarlov score and Basso, Beatie, and Bresnahan functional score, inhibit apoptosis, inflammatory response, and oxidative condition after SCI. The expression level of gp130/JAK/STAT axis was suppressed by BYHWD. BYHWD might be a new therapeutic strategy for the prevention or treatment of SCI.

Nervonic acid improves liver inflammation in a mouse model of Parkinson's disease by inhibiting proinflammatory signaling pathways and regulating metabolic pathways.

BACKGROUND: Nervonic acid (NA) - a type of bioactive fatty acid that is found in natural sources - can inhibit inflammatory reactions and regulate immune system balance. Therefore, the use of NA for the treatment of neurodegenerative diseases has received considerable attention. Our previous study found that NA inhibited inflammatory responses in the brain of Parkinson's disease (PD) mouse models. In addition to the brain, PD is also associated with visceral organ dysfunction, especially impaired liver function. Thus, studying the role of NA in PD-mediated inflammation of the liver is particularly important. METHODS: A combined transcriptome and metabolomic approach was utilized to investigate the anti-inflammatory effects of NA on the liver of PD mice. Inflammatory signaling molecules and metabolic pathway-related genes were examined in the liver using real-time PCR and western blotting. RESULTS: Liver transcriptome analysis revealed that NA exerted anti-inflammatory effects by controlling several pro-inflammatory signaling pathways, such as the down-regulation of the tumor necrosis factor and nuclear factor kappa B signaling pathways, both of which were essential in the development of inflammatory disease. In addition, liver metabolomic results revealed that metabolites related to steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism were up-regulated and those related to valine, leucine, and isoleucine degradation pathways were down-regulated in NA treatment groups compared with the PD model. The integration of metabolomic and transcriptomic results showed NA significantly exerted its anti-inflammatory function by regulating the transcription and metabolic pathways of multiple genes. Particularly, linoleic acid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis were the crucial pathways of the anti-inflammatory action of NA. Key genes in these metabolic pathways and key molecules in inflammatory signaling pathways were also verified, which were consistent with transcriptomic results. CONCLUSION: These findings provide novel insights into the liver protective effects of NA against PD mice. This study also showed that NA could be a useful dietary element for improving and treating PD-induced liver inflammation.

DMC (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone) enhances exercise tolerance via the AMPK-SIRT1-PGC-1α pathway in mice fed a high-fat diet.

Obesity is caused by an imbalance between energy intake and energy expenditure. This study aimed to determine the effects and mechanisms of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) on exercise tolerance in high-fat diet (HFD)-fed mice. Male C57BL/6J mice were randomly divided into two categories (7 groups [n = 8]): sedentary (control [CON], HFD, 200 mg/kg DMC, and 500 mg/kg DMC) and swimming (HFD, 200 mg/kg DMC, and 500 mg/kg DMC). Except the CON group, all other groups were fed HFD with or without DMC intervention for 33 days. The swimming groups were subjected to exhaustive swimming (three sessions/week). Changes in swimming time, glucolipid metabolism, body composition, biochemical indicators, histopathology, inflammation, metabolic mediators, and protein expression were assessed. DMC combined with regular exercise improved endurance performance, body composition, glucose and insulin tolerance, lipid profile, and the inflammatory state in a dose-dependent manner. Further, DMC alone or combined with exercise could restore normal tissue morphology, reduce fatigue-associated markers, and boost whole-body metabolism and the protein expression of phospho-AMP-activated protein kinase alpha/total-AMP-activated protein kinase alpha (AMPK), sirtuin-1 (SIRT1), peroxisome-proliferator-activated receptor gamma coactivator 1alpha (PGC-1α), and peroxisome proliferator-activated receptor alpha in the muscle and adipose tissues of HFD-fed mice. DMC exhibits antifatigue effects by regulating glucolipid catabolism, inflammation, and energy homeostasis. Furthermore, DMC exerts a synergistic exercise-related metabolic effect via the AMPK-SIRT1-PGC-1α signaling pathway, suggesting that DMC is a potential natural sports supplement with mimicked or augmented exercise effects for obesity prevention.

N, N-bis (2-hydroxyethyl) malonamide based amidoxime functionalized polymer immobilized in biomembranes for highly selective adsorption of uranium(VI).

Amidoxime compounds have been widely used in metal separation and recovery because of their excellent chelating properties to metal ions, especially to uranium (VI). In this study, N, N-bis (2-hydroxyethyl) malonamide was obtained from ethanolamine and dimethyl malonate, and used to prepare a two-dimensional network polymer, then the obtained polymer was immobilized in an environmentally friendly chitosan biomembrane, which enhanced its stability and hydrophobicity, meanwhile the amidoxime functionalization was achieved by oximation reaction of bromoacetonitrile, the application of the material further extends to uranium (VI) separation in solutions. Due to the synergistic action of amide group and amidoxime group, poly (ethanolamine-malonamide) based amidoxime biomembranes (PEA-AOM) showed extraordinary adsorption effect on uranium (VI), among which the saturation adsorption capacity of PEA-AOM-2 was 748.64 mg/g. PEA-AOM-2 also had good reusability (following five cycles of adsorption-desorption, the recovery rate maintained at 88%) and selectivity for uranium (VI), showing satisfactory results in competitive ion coexistence system and simulated seawater experiments. This study demonstrated that PEA-AOM-2 provided a new option for uranium (VI) separation in complex environment and low-concentration uranium background.