Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway.

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Complete Restoration of Hearing Loss and Cochlear Synaptopathy via Minimally Invasive, Single-Dose, and Controllable Middle Ear Delivery of Brain-Derived Neurotrophic Factor-Poly(dl-lactic acid-co-glycolic acid)-Loaded Hydrogel.

Noise-induced hearing loss (NIHL) often accompanies cochlear synaptopathy, which can be potentially reversed to restore hearing. However, there has been little success in achieving complete recovery of sensorineural deafness using nearly noninvasive middle ear drug delivery before. Here, we present a study demonstrating the efficacy of a middle ear delivery system employing brain-derived neurotrophic factor (BDNF)-poly-(dl-lactic acid-co-glycolic acid) (PLGA)-loaded hydrogel in reversing synaptopathy and restoring hearing function in a mouse model with NIHL. The mouse model achieved using the single noise exposure (NE, 115 dBL, 4 h) exhibited an average 20 dBL elevation of hearing thresholds with intact cochlear hair cells but a loss of ribbon synapses as the primary cause of hearing impairment. We developed a BDNF-PLGA-loaded thermosensitive hydrogel, which was administered via a single controllable injection into the tympanic cavity of noise-exposed mice, allowing its presence in the middle ear for a duration of 2 weeks. This intervention resulted in complete restoration of NIHL at frequencies of click, 4, 8, 16, and 32 kHz. Moreover, the cochlear ribbon synapses exhibited significant recovery, whereas other cochlear components (hair cells and auditory nerves) remained unchanged. Additionally, the cochlea of NE treated mice revealed activation of tropomyosin receptor kinase B (TRKB) signaling upon exposure to BDNF. These findings demonstrate a controllable and minimally invasive therapeutic approach that utilizes a BDNF-PLGA-loaded hydrogel to restore NIHL by specifically repairing cochlear synaptopathy. This tailored middle ear delivery system holds great promise for achieving ideal clinical outcomes in the treatment of NIHL and cochlear synaptopathy.

The Efficacy of Traditional Chinese Herbal Medicine Across Multiple Cardiovascular Diseases: An Umbrella Review of Systematic Reviews of Randomized Controlled Trials.

ABSTRACT: Traditional Chinese herbal medicine (CHM) has been extensively used in cardiovascular disease (CVD) in modern clinical practice, alone or in combination with conventional treatment. However, its efficacy has not been assessed extensively. From inception until August 2023, we systematically searched 5 public literature databases to conduct the umbrella review. The inclusion criterion is systematic reviews of randomized controlled trials investigating the effect of CHM in the contemporary management of CVDs. The quality of the included systematic reviews, the certainty of the evidence, and the potential risk of bias were assessed. Five hundred and thirty-nine systematic reviews, including 346 studies in Chinese and 193 in English, were selected before the quantitative synthesis. The methodological quality was generally moderate, with a median value of 11. The favorable efficacy of CHM was primarily presented on 5 main conditions: coronary artery disease, hypertension, heart failure, restenosis, and angina pectoris. CHM, with or without conventional treatment, showed a consistent beneficial effect in various CVDs. Nevertheless, the magnitude of the effect requires further investigation as the lack of relevant research and the complexity of the clinical practice of CHM.

Herbal medicine for Hashimoto's thyroiditis: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventional treatments for Hashimoto's thyroiditis (HT) are limited. Herbal medicines (HM) are considered a potential intervention for the treatment of HT. AIM OF THE STUDY: This study aimed to investigate the efficacy and safety of HM for HT. MATERIALS AND METHODS: A Bayesian network meta-analysis was conducted for patients with HT in randomized controlled trials identified in PubMed, Cochrane Library, Web of Science, EMBASE, Chinese Clinical Trial Registry (Chi CTR), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (the VIP), China Chinese Biomedical Database (CBM), and Wanfang Database were searched from their inception to Oct 1, 2022. Outcomes included the primary outcome (TPOAb), secondary outcomes (TSH, TGAb, FT3, FT4, and traditional Chinese medicine symptom scores), and adverse events. This study was registered in PROSPERO (CRD42022363640). RESULTS: Sixteen trials were reviewed and 16 HM formulae were compared. Compared with non-drug therapy (NDT), all therapies, except for Tiaoqi-Qingjie Therapy, reduced the primary outcome of TPOAb with different levels of effectiveness, ranging from 0.01 (95%CI 0.00, 0.02) to 0.92 (95%CI 0.56, 1.53). Ranking probability analysis indicated that Yiqi Huayu Recipe, Liqi Xiaoying decoction, and Shugan Sanjie therapy reduced thyroid antibody levels the most, including TPOAb (100.0%, 90.9%, and 90.3%, respectively) and TGAb (98.3%, 94.4%, and 87.3%, respectively). All HMs displayed a significant effect on the TCM Symptom score and possibly benefitted the treatment of HT, ranging from 6.62 (95% CI 2.06, 21.24) to 94.50 (95% CI 15.97, 559.14). No serious adverse events were reported. CONCLUSIONS: Herbal medicines may be effective in the treatment of HT, especially in reducing thyroid antibody levels and improving clinical symptoms without affecting thyroid function. However, these results should be considered preliminary and further verified using high-quality evidence.

Genetically determined circulating micronutrients and the risk of nonalcoholic fatty liver disease.

Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (ß-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher ß­carotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (PFDR = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05-1.29; P = 0.006, PFDR = 0.028), selenium (OR 1.11, 95% CI 1.03-1.20; P = 0.005, PFDR = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03-1.13; P = 0.002, PFDR = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (Pheterogeneity > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism.

SincMSNet: a Sinc filter convolutional neural network for EEG motor imagery classification.

Objective.Motor imagery (MI) is widely used in brain-computer interfaces (BCIs). However, the decode of MI-EEG using convolutional neural networks (CNNs) remains a challenge due to individual variability.Approach.We propose a fully end-to-end CNN called SincMSNet to address this issue. SincMSNet employs the Sinc filter to extract subject-specific frequency band information and utilizes mixed-depth convolution to extract multi-scale temporal information for each band. It then applies a spatial convolutional block to extract spatial features and uses a temporal log-variance block to obtain classification features. The model of SincMSNet is trained under the joint supervision of cross-entropy and center loss to achieve inter-class separable and intra-class compact representations of EEG signals.Main results.We evaluated the performance of SincMSNet on the BCIC-IV-2a (four-class) and OpenBMI (two-class) datasets. SincMSNet achieves impressive results, surpassing benchmark methods. In four-class and two-class inter-session analysis, it achieves average accuracies of 80.70% and 71.50% respectively. In four-class and two-class single-session analysis, it achieves average accuracies of 84.69% and 76.99% respectively. Additionally, visualizations of the learned band-pass filter bands by Sinc filters demonstrate the network's ability to extract subject-specific frequency band information from EEG.Significance.This study highlights the potential of SincMSNet in improving the performance of MI-EEG decoding and designing more robust MI-BCIs. The source code for SincMSNet can be found at:https://github.com/Want2Vanish/SincMSNet.

A Preliminary Study on Warm Acupuncture and Moxibustion for Treating Chronic Obstructive Pulmonary Disease with Abdominal Distension.

Most patients with COPD have a combination of abdominal distension, which has been shown to adversely affect pulmonary symptoms, frequency of acute exacerbations, and quality of life in patients with COPD. Warm acupuncture and moxibustion have been shown to be effective in relieving symptoms in patients with COPD combined with abdominal distention. Warm acupuncture and moxibustion are highly effective, easy to perform, and inexpensive forms of traditional Chinese medicine treatments. The standardized practice of warm acupuncture and moxibustion is very important for the treatment of COPD combined with abdominal distension. The specific steps include selecting the appropriate acupoints for needling through syndrome differentiation treatment and selecting moxa sticks of appropriate length for moxibustion for about 30 min after the De-qi. The course of treatment lasts for one week. The following indicators are specifically assessed: the score of the COPD Assessment Test (CAT) and the abdominal distension visual analog scale (VAS). This article will clearly illustrate how to standardize the manipulation of warm acupuncture and moxibustion to relieve COPD combined with abdominal distention.

[Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS].

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

[Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model].

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1ß and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1ß, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

A Traditional Chinese Medicine Characteristic Therapy for Bronchial Asthma: Moxibustion.

Bronchial asthma is a chronic inflammatory disease of the airway which can lead to symptoms such as recurrent wheezing, shortness of breath, chest tightness, or cough, as a result of increased airway reactivity. With high diurnal variation, these symptoms often occur or worsen at night or in the morning. By burning and roasting the Chinese medica above human acupoints, moxibustion is a type of treatment that stimulates the activity of the human meridians through drugs and heat stimulation to prevent and treat diseases. According to the principle of syndrome differentiation and treatment of traditional Chinese medicine, acupoints are selected on the corresponding parts, which has a definite effect. It is regarded as a characteristic traditional Chinese medicine therapy for bronchial asthma. This protocol elaborates the methods and steps of patient management, material preparation, selection of acupoints, operation, and postoperative nursing to ensure safe and effective moxibustion treatment to significantly improve the clinical symptoms and quality of life of patients with bronchial asthma.

Traditional Chinese medicine monomers: Targeting pulmonary artery smooth muscle cells proliferation to treat pulmonary hypertension.

Pulmonary hypertension (PH) is a complex multifactorial disease characterized by increased pulmonary vascular resistance and pulmonary vascular remodeling (PVR), with high morbidity, disability, and mortality. The abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main pathological change causing PVR. At present, clinical treatment drugs for PH are limited, which can only improve symptoms and reduce hospitalization but cannot delay disease progression and reduce survival rate. In recent years, numerous studies have shown that traditional Chinese medicine monomers (TCMs) inhibit excessive proliferation of PASMCs resulting in alleviating PVR through multiple channels and multiple targets, which has attracted more and more attention in the treatment of PH. In this paper, the experimental evidence of inhibiting PASMCs proliferation by TCMs was summarized to provide some directions for the future development of these mentioned TCMs as anti-PH drugs in clinical.

Water source of Robinia pseudoacacia and Platycladus orientalis plantations under different soil moisture conditions in the Loess Plateau of Western Shanxi, China.

Water is a key factor limiting plant growth in loess regions. Studying water use by different afforestation species under different water conditions is crucial to understand the drought resistance mechanisms of plants in arid and semi-arid regions. We analyzed water use at different depths by the afforestation species Robinia pseudoacacia and Platycladus orientalis under the drought treatment (100% no throughfall, DT) and the natural rainfall (control, CK) by stable isotope (δ18O, δ2H) technique and explored their drought adaptability. The results showed that R. pseudoacacia mainly absorbed soil water at 0-40 cm soil layer in the wet months (June and September), with a contribution rate of 68.0%±2.4%, and at four layers (0-10, 10-40, 40-60, and 60-120 cm) evenly in the dry months (July and August) in the CK. In contrast, P. orientalis mainly absorbed soil water at 0-40 cm layer in both the wet and dry months, with the contribution rate being 77.0%±2.4% and 57.4%±3.0%, respectively. In the DT, the water-use depths of R. pseudoacacia and P. orientalis tended to move downward with the decreases of soil water content. The water-use depths of R. pseudoacacia changed from 0-40 cm to 60-120 cm, while that of P. orientalis changed from 0-40 cm to the four layers mentioned evenly. R. pseudoacacia and P. orientalis could adjust water-use depths under different water conditions and showed strong drought adaptability, a feature of great significance for evaluating the stress resistance and stability of local plantations.

V.I.P. Score: A Comprehensive Grading System to Predict Difficulty of HoLEP Procedure for Small-to-Moderate Sized Prostate (<120 mL).

OBJECTIVE: To develop a comprehensive scoring system in addition to the conventionally used prostatic volume (PV), for predicting the difficulty of holmium laser enucleation of the prostate (HoLEP) that may arise with small-to-moderate sized prostate. METHODS: We retrospectively reviewed 151 consecutive patients who underwent HoLEP and had a PV less than 120 mL. Based on previous literature, a difficult procedure was defined as a prolonged operative time (OT>90 minute) in 88 cases, while the control group (OT≤90 minute) consisted of 63 patients. The clinical data, including age, body mass index, PV, intravesical prostatic protrusion (IPP), prostate specific antigen (PSA), prostate specific antigen density, urinary tract infection, microscopic hematuria, prior biopsy, diabetes mellitus, hypertension, history of acute urinary retention, catheter dependency and use of antiplatelet / anticoagulation drugs or 5-alpha reductase inhibitor were compared between the 2 groups. RESULTS: Univariate analysis revealed significant differences between the 2 groups. Multivariate analysis identified 3 main independent predictors for difficulty, including volume (V) (60-90 mL OR = 9.812, P < .001) (≥90 mL OR = 18.173, P = .01), IPP (I) (OR = 3.157, P = .018), and PSA (P) (≥4 ng/ml OR = 16.738, P < .001). Therefore, a V.I.P. score was developed based on the regression model and ranged from 0 to 7 points. The area under the curve showed preferable predictive ability of the V.I.P. score compared to PV (0.906 vs 0.869). CONCLUSION: We developed a V.I.P. score that can accurately predict the difficulty of the HoLEP procedure for PV less than 120 mL in order to optimize clinical outcomes.

Supplementation with Natto and Red Yeast Rice Alters Gene Expressions in Cholesterol Metabolism Pathways in ApoE-/- Mice with Concurrent Changes in Gut Microbiota.

We aimed to examine the effect of natto and red yeast rice (NR) supplementation on lipid and lipoprotein profiles, gene expressions of cholesterol metabolism, and the composition of gut microbiota in ApoE-/- mice. Forty-one male ApoE-/- mice aged 7-8 wks old were randomly fed a control diet (CD), CD + NR (oral gavage at 0.3 g/kg BW/day), high-fat and high-cholesterol diet (HFD), or HFD + NR for 12 wks. Fasting blood samples, liver and intestine tissues and fecal samples were collected at week 12. Biochemical parameters, gene expressions in cholesterol metabolism and gut microbiota composition and diversity were measured using standard methods. NR supplementation had no significant effect on lipid and lipoprotein profiles. Compared with the HFD group, HFD + NR resulted in higher mRNA expressions of HMGCR and CYP7A1 (both P-NR < 0.05) and ABCA1 (P-diet*NR = 0.0134, P-NR = 0.0407), lower mRNA expression of PCSK9 (P-diet*NR = 0.0002), lower fasting glucose concentrations (P-diet*NR = 0.0011), and lower relative abundance of genera Bacteroides and Lactococcus (both P-NR < 0.01) and Coriobacteriaceae_UCG-002 (P-diet*NR = 0.0007). The relative abundance of Lactococcus was inversely correlated with HMGCR and CYP7A1, and the relative abundance of Coriobacteriaceae_UCG-002 was positively correlated with PCSK9 and inversely correlated with ABCA1 (all P < 0.05). These findings suggest that NR supplementation may regulate gene expressions in cholesterol metabolism via changes in the gut microbiota in HFD-fed ApoE-/- mice.

Radix Panacis quinquefolii Extract Ameliorates Inflammatory Bowel Disease through Inhibiting Inflammation.

OBJECTIVE: To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). METHODS: The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. RESULTS: Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01). CONCLUSION: RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway.

OBJECTIVE: To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish. METHODS: The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe. RESULTS: The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae. CONCLUSION: KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

FBMSNet: A Filter-Bank Multi-Scale Convolutional Neural Network for EEG-Based Motor Imagery Decoding.

OBJECT: Motor imagery (MI) is a mental process widely utilized as the experimental paradigm for brain-computer interfaces (BCIs) across a broad range of basic science and clinical studies. However, decoding intentions from MI remains challenging due to the inherent complexity of brain patterns relative to the small sample size available for machine learning. APPROACH: This paper proposes an end-to-end Filter-Bank Multiscale Convolutional Neural Network (FBMSNet) for MI classification. A filter bank is first employed to derive a multiview spectral representation of the EEG data. Mixed depthwise convolution is then applied to extract temporal features at multiple scales, followed by spatial filtering to mitigate volume conduction. Finally, with the joint supervision of cross-entropy and center loss, FBMSNet obtains features that maximize interclass dispersion and intraclass compactness. MAIN RESULTS: We compare FBMSNet with several state-of-the-art EEG decoding methods on two MI datasets: the BCI Competition IV 2a dataset and the OpenBMI dataset. FBMSNet significantly outperforms the benchmark methods by achieving 79.17% and 70.05% for four-class and two-class hold-out classification accuracy, respectively. SIGNIFICANCE: These results demonstrate the efficacy of FBMSNet in improving EEG decoding performance toward more robust BCI applications. The FBMSNet source code is available at https://github.com/Want2Vanish/FBMSNet.

Dietary fish and omega-3 polyunsaturated fatty acids intake and cancer survival: A systematic review and meta-analysis.

Fish and omega-3 polyunsaturated fatty acids (PUFA) have been suggested to play a role in improving cancer prognosis. However, results from epidemiological studies remain inconsistent. Here we assess the association between dietary fish and/or omega-3 PUFAs intake and cancer prognosis with meta-analysis of observational studies. A systematic search of related publications was performed using PubMed and Web of Science databases. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted and then pooled using a random-effect model. Potential linear and non-linear dose-response relationships were explored using generalized least squares estimation and restricted cubic splines. As a result, 21 cohort studies were included in our analysis. Compared to the lowest category, the highest category of fish intake was associated with a significant lower mortality in patients with ovarian cancer (n = 1, HR = 0.74, 95% CI: 0.57-0.95) and overall cancer (n = 12, HR = 0.87, 95% CI: 0.81-0.94). Marine omega-3 PUFAs intake rather than total omega-3 PUFAs intake showed significant protective effects on survival of overall cancer (n = 8, HR = 0.81, 95% CI: 0.71-0.94), in particular prostate cancer (n = 2, HR = 0.62, 95% CI: 0.46-0.82). Dose-response meta-analysis indicated a nonlinear and a linear relationship between fish intake, as well as marine omega-3 PUFAs intake, and overall cancer survival, respectively. In conclusion, our analysis demonstrated a protective effect of dietary fish and marine omega-3 PUFAs consumption on cancer survival.