Huang Lian Jie Du Decoction enhances the anti-tumor efficacy of immune checkpoint inhibitors by activating TLR7/8 signalling in melanoma.

BACKGROUND: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. METHODS: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. RESULTS: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. CONCLUSIONS: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.

Warfarin-A natural anticoagulant: A review of research trends for precision medication.

BACKGROUND: Warfarin is a widely prescribed anticoagulant in the clinic. It has a more considerable individual variability, and many factors affect its variability. Mathematical models can quantify the quantitative impact of these factors on individual variability. PURPOSE: The aim is to comprehensively analyze the advanced warfarin dosing algorithm based on pharmacometrics and machine learning models of personalized warfarin dosage. METHODS: A bibliometric analysis of the literature retrieved from PubMed and Scopus was performed using VOSviewer. The relevant literature that reported the precise dosage of warfarin calculation was retrieved from the database. The multiple linear regression (MLR) algorithm was excluded because a recent systematic review that mainly reviewed this algorithm has been reported. The following terms of quantitative systems pharmacology, mechanistic model, physiologically based pharmacokinetic model, artificial intelligence, machine learning, pharmacokinetic, pharmacodynamic, pharmacokinetics, pharmacodynamics, and warfarin were added as MeSH Terms or appearing in Title/Abstract into query box of PubMed, then humans and English as filter were added to retrieve the literature. RESULTS: Bibliometric analysis revealed important co-occuring MeShH and index keywords. Further, the United States, China, and the United Kingdom were among the top countries contributing in this domain. Some studies have established personalized warfarin dosage models using pharmacometrics and machine learning-based algorithms. There were 54 related studies, including 14 pharmacometric models, 31 artificial intelligence models, and 9 model evaluations. Each model has its advantages and disadvantages. The pharmacometric model contains biological or pharmacological mechanisms in structure. The process of pharmacometric model development is very time- and labor-intensive. Machine learning is a purely data-driven approach; its parameters are more mathematical and have less biological interpretation. However, it is faster, more efficient, and less time-consuming. Most published models of machine learning algorithms were established based on cross-sectional data sourced from the database. CONCLUSION: Future research on personalized warfarin medication should focus on combining the advantages of machine learning and pharmacometrics algorithms to establish a more robust warfarin dosage algorithm. Randomized controlled trials should be performed to evaluate the established algorithm of warfarin dosage. Moreover, a more user-friendly and accessible warfarin precision medicine platform should be developed.

Application and Value of Limbs Peripheral Nerve Ultrasound in Guillain-Barre Syndrome.

Background: At present, some Guillain-Barre syndrome (GBS) patients have a relatively poor prognosis due to the lack of timely diagnosis, and the risk of death is difficult to reduce. At present, the level of clinical diagnosis of GBS is not ideal, and the time of clinical examination and diagnosis is relatively long. How to improve the level of clinical diagnosis, clinical treatment and prognosis of GBS has always been the focus of clinical research of GBS. This study mainly analyzes the application efficacy of limb peripheral nerve ultrasound in the diagnosis, classification and disease assessment of GBS, hoping to supplement the application research of limb peripheral nerve ultrasound in the diagnosis of GBS and provide some reference for the development of clinical diagnosis of GBS. Objective: To explore the application and value of limb peripheral nerve ultrasound in Guillain-Barre syndrome (GBS). Methods: In this case-control study, 35 GBS patients (GBS group) and 20 healthy volunteers (normal group) were enrolled, the ultrasound features of GBS, NCSA dimensions of limbs, NCSA sizes of limbs in patients with different types of GBS, and NCSA sizes of vagus nerves in patients with different conditions of GBS were clinically detected and collected.Pearson correlation coefficient was used to evaluate the correlation between limb nerve cross-sectional areas (NCSAs) and nerve electrophysiology indexes in GBS patients. The receiver operating characteristic curve (ROC) was adopted to analyze the value of limb NCSAs for diagnosing GBS. Results: Compared with the normal group, NCSAs of multiple limbs neurodes in the GBS group increased significantly (P < .05). Patients with different GBS classifications had significantly different limb NCSAs in the proximal or distal nerve (P < .05). Compared with patients without autonomic nervous dysfunction, patients combined with autonomic nervous dysfunction had significantly expanded NCSA of the vagus nerve (P < .05). NCSAs of the median nerve and ulnar nerve were negatively correlated with motor nerve conduction velocity (MCV) and positively correlated with compound muscle action potential (CMAP) latency (both P < .05); NCSA of the median nerve showed a negative correlation with sensory nerve conduction velocity (SCV) (P < .05).The ROC curve showed that the auc of ncsa of median nerve (median), ulnar nerve (proximal), vagus nerve, brachial plexus, and common peroneal nerve in the diagnosis of GBS were 0.851, 0.813, 0.783, 0.774, and 0.670, respectively (P < .05), which had diagnostic efficacy. The sensitivity were 85.36%, 80.08%, 78.85%, 76.93% and 70.88%, respectively. The specificity were 68.29%, 73.65%, 78.86%, 80.29% and 83.56%, respectively. Conclusion: Limbs peripheral nerve ultrasound can effectively assist the early diagnosis, classification, and assessment of the severity of illness of GBS, it has a good diagnostic effect on multi-limb ganglion NCSA and vagus nerve NCSA.In the future, the application of limb peripheral nerve ultrasound in the early diagnosis, classification and severity assessment of GBS can improve the efficacy of clinical diagnosis of GBS and provide a good basis for the improvement of prognosis of GBS.

Enhanced indigenous consortia for the remediation of uranium-contaminated groundwater by bioaugmentation: Reducing and phosphate-solubilizing consortia.

To investigate the strengthening effects and mechanisms of bioaugmentation on the microbial remediation of uranium-contaminated groundwater via bioreduction coupled to biomineralization, two exogenous microbial consortia with reducing and phosphate-solubilizing functions were screened and added to uranium-contaminated groundwater as the experimental groups (group B, reducing consortium added; group C, phosphate-solubilizing consortium added). ß-glycerophosphate (GP) was selected to stimulate the microbial community as the sole electron donor and phosphorus source. The results showed that bioaugmentation accelerated the consumption of GP and the proliferation of key functional microbes in groups B and C. In group B, Dysgonomonas, Clostridium_sensu_stricto_11 and Clostridium_sensu_stricto_13 were the main reducing bacteria, and Paenibacillus was the main phosphate-solubilizing bacteria. In group C, the microorganisms that solubilized phosphate were mainly unclassified_f_Enterobacteriaceae. Additionally, bioaugmentation promoted the formation of unattached precipitates and alleviated the inhibitory effect of cell surface precipitation on microbial metabolism. As a result, the formation rate of U-phosphate precipitates and the removal rates of aqueous U(VI) in both groups B and C were elevated significantly after bioaugmentation. The U(VI) removal rate was poor in the control group (group A, with only an indigenous consortium). Propionispora, Sporomusa and Clostridium_sensu_stricto_11 may have played an important role in the removal of uranium in group A. Furthermore, the addition of a reducing consortium promoted the reduction of U(VI) to U(IV), and immobilized uranium existed in the form of U(IV)-phosphate and U(VI)-phosphate precipitates in group B. In contrast, U was present mainly as U(VI)-phosphate precipitates in groups A and C. Overall, bioaugmentation with an exogenous consortium resulted in the rapid removal of uranium from groundwater and the formation of U-phosphate minerals and served as an effective strategy for improving the treatment of uranium-contaminated groundwater in situ.

The regulation of tolerogenic dendritic cells by a Chinese herb formula improves abortion prone in mice.

BACKGROUND: Abortion prone (AP) is a common clinical event. The underlying mechanism remains unclear. Traditional Chinese formulas are known to be efficient in the management of abortion. The purpose of this study is to observe the effects of Anzitiaochongtang (AZT), a traditional formulation of Chinese medicine, on improving AP in mice by regulating immune tolerance. METHODS: An established abortion model (CBA/J×DBA/2) was employed. AZT was prepared and administered to mice in a manner consistent with clinical practice. Tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cell) in mice were analyzed by immunological approaches to be used as representative immune tolerant parameters. RESULTS: An AP model was established with CBA/J × DBA/2 mice. The expression of IL-10 in tDC and Tr1 cell frequency in the mouse decidua tissues were lower in the AP group than that in the normal pregnancy (NP) group. Administration of AZT up regulated the expression of IL-10 in tDCs and Tr1 cell generation in the decidua tissues, and improved the pregnancy and tissue structure in AP mice. The main mechanism by which AZT improves pregnancy in AP mice is that AZT enhanced the expression of galectin-9 in the epithelial cells of decidua tissues. Galectin 9 activates TIM3 on DCs to promote the IL-10 expression. The DCs induced more Tr1 cells in the decidua tissues. CONCLUSIONS: Dysfunctional tDCs were detected in the AP decidua tissues. Administration of AZT improved pregnancy in AP mice by regulating tDC function and generation of Tr1 cells in the maternal-fetal interface.

Fucoxanthin, a marine derived carotenoid, attenuates surgery-induced cognitive impairments via activating Akt and ERK pathways in aged mice.

BACKGROUND: Fucoxanthin is the most abundant marine carotenoid derived from brown seaweeds, possesses antioxidant, anti-inflammatory, and neuroprotective properties, and might be benefit for the treatment of neurological disorders. Post-operative cognitive dysfunction (POCD) is a neurological symptom with learning and memory impairments, mainly affecting the elderly after surgery. However, there is no effective treatments for this symptom. PURPOSES: In this study, we evaluated the neuroprotective effects of fucoxanthin against POCD in aged mice after surgery. STUDY DESIGN AND METHODS: The animal model of POCD was established in 12 - 14 month aged mice with a laparotomy. Curcumin was used as a positive control. The beneficial effects of fucoxanthin on POCD was analyzed by behavioral tests. Pro-inflammatory cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA). And the expressions of key proteins in the Akt and ERK signaling pathways were analyzed by Western blotting analysis. The morphology of microglial cells and astrocytes was explored by immunohistochemical staining. The activity of antioxidant superoxide dismutase (SOD) and catalase (CAT) were measured by anti-oxidative enzyme activity assays. RESULTS: Fucoxanthin at 100 - 200 mg/kg significantly attenuated cognitive dysfunction, with a similar potency as curcumin, in aged mice after surgery. In addition, fucoxanthin and curcumin significantly increased the expression of pAkt, prevented the activation of microglial cells and astrocytes, and inhibited the secretion of pro-inflammatory interleukin-1ß (IL - 1ß) and tumor necrosis factor-α (TNF-α). Furthermore, fucoxanthin and curcumin elevated the ERK pathway and potently increased the activity of antioxidant enzymes. Most importantly, U0126, an inhibitor of the ERK pathway, and wortmannin, an inhibitor of the Akt pathway, significantly abolished the cognitive-enhancing effects, as well as the inhibition of neuroinflammation and the reduction of oxidative stress, induced by fucoxanthin in aged mice after surgery. CONCLUSION: Fucoxanthin might be developed as a functional food or drug for the treatment of POCD by inhibiting neuroinflammation and enhancing antioxidant capacity via the activation of the Akt and ERK signaling pathways.

Near-Infrared Self-Assembled Hydroxyl Radical Generator Based on Photoinduced Cascade Electron Transfer for Hypoxic Tumor Phototherapy.

The hydroxyl radical (•OH) is an extremely potent reactive oxygen species that plays a crucial role in photooxidations within the realm of hypoxic tumor therapy. However, the current methods for •OH photogeneration typically rely on inorganic materials that require UV/vis light excitation. Consequently, photogenerators based on organic molecules, especially those utilizing near-infrared (NIR) light excitation, are rare. In this study, the concept of photoinduced cascade charge transfer (PICET), which utilizes NIR heavy-atom-free photosensitizers (ANOR-Cy5) to generate •OH is introduced. The ANOR-Cy5 photosensitizer, with its flexible hydrophobic structure, enables the formation of nanoparticles in aqueous solutions through molecular assembly. PICET involves a symmetry-breaking charge separation-induced localized charge-separated state, transitioning to a delocalized charge-separated state, which governs the efficiency of •OH generation. Thanks to the oxygen-independent nature of •OH generation and its robust oxidative properties, the ANOR-Cy5-based photosensitizer demonstrates highly effective photoinduced anti-cancer effects, even under severely hypoxic conditions. This discovery emphasizes the potential for achieving •OH photogeneration using a single organic molecule through the engineering of molecular self-assembly, thereby opening up new possibilities for phototherapy and beyond.

Nanopeptide C-I20 as a novel feed additive effectively alleviates detrimental impacts of soybean meal on mandarin fish by improving the intestinal mucosal barrier.

Antibacterial peptide has been widely developed in cultivation industry as feed additives. However, its functions in reducing the detrimental impacts of soybean meal (SM) remain unknown. In this study, we prepared nano antibacterial peptide CMCS-gcIFN-20H (C-I20) with excellent sustained-release and anti-enzymolysis, and fed mandarin fish (Siniperca chuatsi) with a SM diet supplemented with different levels of C-I20 (320, 160, 80, 40, 0 mg/Kg) for 10 weeks. 160 mg/Kg C-I20 treatment significantly improved the final body weight, weight gain rate and crude protein content of mandarin fish and reduced feed conversion ratio. 160 mg/Kg C-I20-fed fish maintained appropriate goblet cells number and mucin thickness, as well as improved villus length, intestinal cross-sectional area. Based on these advantageous physiological changes, 160 mg/Kg C-I20 treatment effectively reduced multi-type tissue (liver, trunk kidney, head kidney and spleen) injury. The addition of C-I20 did not change the muscle composition and muscle amino acids composition. Interestingly, dietary 160 mg/Kg C-I20 supplementation prevented the reduction in myofiber diameter and change in muscle texture, and effectively increased polyunsaturated fatty acids (especially DHA + EPA) in muscle. In conclusion, dietary C-I20 in a reasonable concentration supplementation effectively alleviates the negative effects of SM by improving the intestinal mucosal barrier. The application of nanopeptide C-I20 is a prospectively novel strategy for promoting aquaculture development.

The photocatalytic reduction of U(VI) by Ag-doped SnS2 materials under visible light.

Efficient degradation of uranium(VI) (U(VI)) in wastewater is an urgent problem because of the chemical toxicity and radiotoxicity. In this study, the Agx-SnS2 photocatalysts were compounded by a simple hydrothermal method, effectively removing U(VI) under visible light in water. Compared with SnS2, the results indicated that Agx-SnS2 would decrease the crystallinity without destroying the crystal structure. Moreover, it has excellent photocatalytic performance on the degradation rate of U(VI). Ag0.5-SnS2 exhibited a prominent photocatalytic reduction efficiency of UO22+ of about 86.4% under optical light for 75 min. This was attributed to Ag-doped catalysts, which can narrow the band gap and enhance absorption in visible light. Meanwhile, the doping of Ag promoted the separation of photoinduced carriers, so that more photogenerated charges participated in the photocatalytic reaction. The stability and reusability were verified by the cycle test and the potential photocatalytic mechanism was analyzed based on the experiment.

Icariside II potentiates the anti-PD-1 antitumor effect by reducing chemotactic infiltration of myeloid-derived suppressor cells into the tumor microenvironment via ROS-mediated inactivation of the SRC/ERK/STAT3 signaling pathways.

BACKGROUND: Immune checkpoint blockade agents, such as anti-PD-1 antibodies, show promising antitumor efficacy but only a limited response in patients with non-small cell lung cancer (NSCLC). Icariside II (IS), a metabolite of Herba Epimedii, is a COX-2 and EGFR inhibitor that can enhance the anti-PD-1 effect. This study aimed to evaluate the antitumor effect of IS in combination with anti-PD-1 and explore the underlying mechanism. METHODS: Tumor growth was assessed in Lewis Lung Cancer (LLC) tumor-bearing mice in seven groups (control, IS 20 mg/kg, IS 40 mg/kg, anti-PD-1, IS 20 mg/kg+anti-PD-1, IS 40 mg/kg+anti-PD-1, ERK inhibitor+anti-PD-1). Tumor-infiltrating immune cells were measured by flow cytometry. The mechanisms were explored by tumor RNA-seq and validated in LLC cells through molecular biological experiments using qRT‒PCR, ELISA, and western blotting. RESULTS: Animal experiments showed that IS in combination with anti-PD-1 further inhibited tumor growth and remarkably reduced the infiltration of myeloid-derived suppressor cells (MDSCs) into the tumor compared with anti-PD-1 monotherapy. RNA-seq and in vitro experiments showed that IS suppressed the chemotactic migration of MDSCs by downregulating the expression of CXC chemokine ligands 2 (CXCL2) and CXCL3. Moreover, IS promoted reactive oxygen species (ROS) generation and inhibited the activation of SRC/ERK/STAT3 in LLC cells, which are upstream signaling pathways of these chemokines. CONCLUSION: IS potentiates the anti-PD-1 anti-tumor effect by reducing chemotactic infiltration of the myeloid-derived suppressor cell into the tumor microenvironment, via ROS-mediated inactivation of SRC/ERK/STAT3 signaling pathways.

Leech-Centipede Granules Suppress EndMT to Improve Erectile Dysfunction in Rats with Diabetes Mellitus via TGF-ß/Smad Pathway.

OBJECTIVE: To investigate whether Leech-Centipede (LC) Granules can improve erectile function in rats with diabetes mellitus-associated erectile dysfunction (DMED) through endothelial-to-mesenchymal transition (EndMT) inhibition. METHODS: Components of LC Granules were identified via ultra-high-performance liquid chromatography. Thirty male Sprague Dawley rats were injected with streptozotocin and fed continuously for 8 weeks to establish the DMED rat model. Rats with erectile dysfunction symptoms diagnosed using apomorphine were divided into DMED and low-, medium-, and high-doses LC groups (n=6 in each). The negative control (NC, n=6) and DMED groups were given 5 mL of deionized water via intragastric gavage, and the low-, medium- and the high-doses LC groups were administered LC at 1.6, 3.2, and 6.4 g/kg, respectively, via intragastric gavage for 4 weeks. The intracavernous pressure (ICP), mean arterial pressure (MAP), and nitric oxide (NO) levels in cavernous tissue were measured for each group. Quantitative reverse transcription-polymerase chain reaction and Western blot were used to detect mRNA and protein expressions of endothelial and mesenchymal markers. Immunofluorescence staining was used to observe α-SMA, and Masson's trichrome staining was performed to determine the myofiber/collagen ratio. RESULTS: A total of 474 active components were identified. After treatment, the ICP/MAP value and NO level were significantly higher in the medium- and high-dose LC groups than in the DMED group (P<0.05). Compared with the DMED groups, the medium- and high-dose groups LC significantly increased and decreased endothelial and mesenchymal markers expression, respectively (P<0.05). Tumor growth factor (TGF)ß R II, p-Smad2, and p-Smad3 levels were considerably higher following diabetes onset but reduced following LC intervention (P<0.05), except for TGF ß 1 (P>0.05). α-SMA expression was significantly higher in the DMED group and was reduced in all LC intervention groups (P>0.05). The myofiber/collagen ratio in the LC groups was higher than that in the DMED group but lower than that in the NC group (all P<0.05). CONCLUSIONS: LC Granules may improve the erectile function of DMED rats by suppressing TGF-ß/Smad pathway to reverse EndMT.

Study on the Effect of Micro-Force Perturbations and Temperature Fluctuation on Interferometer for the Taiji Program.

To increase the interferometric measurement resolution in the Taiji program, we present a noise suppression method in this paper. Taking the specific micro-force perturbation and temperature fluctuation in the Taiji-1 interferometer as an example, we set up and experimentally verified the corresponding transfer function to quantify the effect of both noise sources on the interferometric results. Consistent results were obtained between the numerical and experimental results for the transfer function. It is instructive to eliminate the micro-force perturbations and temperature fluctuations during on-orbit interferometric measurement for as long as the acquisition of the force or temperature distribution of related surfaces and the corresponding transfer functions. This indicates that the method can be used for noise sensing and more in the field of noise elimination and measurement resolution improvement for future Taiji program interferometers.

Genome-wide identification and expression analysis of the calmodulin-binding transcription activator (CAMTA) family genes in tea plant.

BACKGROUND: As a type of calmodulin binding protein, CAMTAs are widely involved in vegetative and reproductive processes as well as various hormonal and stress responses in plants. To study the functions of CAMTA genes in tea plants, we investigated bioinformatics analysis and performed qRT-PCR analysis of the CAMTA gene family by using the genomes of 'ShuChaZao' tea plant cultivar. RESULTS: In this study, 6 CsCAMTAs were identified from tea plant genome. Bioinformatics analysis results showed that all CsCAMTAs contained six highly conserved functional domains. Tissue-specific analysis results found that CsCAMTAs played great roles in mediating tea plant aging and flowering periods. Under hormone and abiotic stress conditions, most CsCAMTAs were upregulated at different time points under different treatment conditions. In addition, the expression levels of CsCAMTA1/3/4/6 were higher in cold-resistant cultivar 'LongJing43' than in the cold-susceptible cultivar 'DaMianBai' at cold acclimation stage, while CsCAMTA2/5 showed higher expression levels in 'DaMianBai' than in 'LongJing43' during entire cold acclimation periods. CONCLUSIONS: In brief, the present results revealed that CsCAMTAs played great roles in tea plant growth, development and stress responses, which laid the foundation for deeply exploring their molecular regulation mechanisms.

Vacancy defect-promoted nanomaterials for efficient phototherapy and phototherapy-based multimodal Synergistic Therapy.

Phototherapy and multimodal synergistic phototherapy (including synergistic photothermal and photodynamic therapy as well as combined phototherapy and other therapies) are promising to achieve accurate diagnosis and efficient treatment for tumor, providing a novel opportunity to overcome cancer. Notably, various nanomaterials have made significant contributions to phototherapy through both improving therapeutic efficiency and reducing side effects. The most key factor affecting the performance of phototherapeutic nanomaterials is their microstructure which in principle determines their physicochemical properties and the resulting phototherapeutic efficiency. Vacancy defects ubiquitously existing in phototherapeutic nanomaterials have a great influence on their microstructure, and constructing and regulating vacancy defect in phototherapeutic nanomaterials is an essential and effective strategy for modulating their microstructure and improving their phototherapeutic efficacy. Thus, this inspires growing research interest in vacancy engineering strategies and vacancy-engineered nanomaterials for phototherapy. In this review, we summarize the understanding, construction, and application of vacancy defects in phototherapeutic nanomaterials. Starting from the perspective of defect chemistry and engineering, we also review the types, structural features, and properties of vacancy defects in phototherapeutic nanomaterials. Finally, we focus on the representative vacancy defective nanomaterials recently developed through vacancy engineering for phototherapy, and discuss the significant influence and role of vacancy defects on phototherapy and multimodal synergistic phototherapy. Therefore, we sincerely hope that this review can provide a profound understanding and inspiration for the design of advanced phototherapeutic nanomaterials, and significantly promote the development of the efficient therapies against tumor.

Development, characterization and in vitro bile salts binding capacity of selenium nanoparticles stabilized by soybean polypeptides.

The paper presents the positive effect of soybean polypeptides (SP) on the stability and the potential hypolipidemic effect of selenium nanoparticles (SeNPs). After preparing SeNPs, SP with different molecular weight were introduced to stabilize SeNPs. We found that the SP with molecular weight >10 kDa (SP5) had the best stabilizing effect on SeNPs. We inferred that the steric resistance resulting from the long chains of SP5 protected SeNPs from collision-mediated aggregation, and the electrostatic repulsions between SP5 and SeNPs also played a positive role in stabilizing SeNPs. The as-prepared SP5-SeNPs were spherical, amorphous and zero valent. It was proved that SeNPs were bound with SP5 through O- and N- groups in SP5, and the main forces were hydrogen bonds and van der Waals forces. The bile salts binding assay showed that the SP5-SeNPs exhibited a high binding capacity to bile salts, which indicated their potential in hypolipidemic application.

Acute effects of mindfulness-based intervention on athlete cognitive function: An fNIRS investigation.

BACKGROUND: Mindfulness-based intervention (MBI) as a psychological treatment is adopted in the sports field, but its effect during competition has not been explored. This study investigated the acute effect of a brief MBI on athletes' cognitive function after a 45-min, lab-based soccer protocol. METHODS: In a single-blind randomized counter-balanced crossover design, 17 male soccer players completed two main trials-an MBI trial and a control trial. The MBI trial was provided with a brief MBI after 45-min exercise; the control trial was instead assigned a travel-related audio to listen to at that time. In each main trial, cognitive function (i.e., Stroop task for inhibition; Corsi-block tapping task for working memory), salivary cortisol, blood lactate and mental fatigue were measured at baseline (pretest) and after the intervention (posttest). The cerebral oxygenation status was recorded using functional near-infrared spectroscopy during the cognitive function test. RESULTS: The brief MBI improved working memory performance in terms of both reaction time (pre vs. post, P = 0.02, d = 0.71) and accuracy (pre vs. post, P = 0.009, d = 0.58), supported by eliciting increased oxyhemoglobin concentration in the prefrontal cortex of the brain. Whereas a slightly better cognitive performance for MBI trial than control trial at posttest (P = 0.37, d = 0.32) accompanied by a lower oxyhemoglobin concentration. A lower mental fatigue level (P = 0.05, d = 0.6) and lower cortisol concentration (P = 0.04, d = 0.65) were observed in the MBI trial than in the control trial after the intervention at posttest. The decreased cortisol concentration correlated with increased inhibition performance in the MBI trial. CONCLUSION: The acute effect of MBI on athletes' mental fatigue and cortisol concentration was detected, and the beneficial effect on working memory was preliminarily supported. In general, MBI is recommended to be adopted at half-time of a soccer game.

Synthesis, characterization of tuna polypeptide selenium nanoparticle, and its immunomodulatory and antioxidant effects in vivo.

The tuna polypeptide (TP) was used as the reducing agent and the stabilizing agent to synthesize a tuna polypeptide selenium nanoparticle (TP-SeNP) via a green method. An animal experiment was conducted to investigate its immunomodulatory and antioxidant effects in vivo. The results indicated that the TP regulated the accumulation and stabilization of the TP-SeNP. And the conversion of selenium was tested to be 20.44%. The TP-SeNP was about 22 nm in diameter, a mix of spherical and quasi-spherical, and amorphous. The reaction between the TP and Na2SeO3 was entropy-driven spontaneous, and the binding force was mainly hydrophobic. Intake of the TP-SeNP could greatly increase the phagocytic activity of the mononuclear phagocytic system, and the contents of immunological molecules. The antioxidant capacity of the liver was also improved.

Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets.

Fucoxanthin, one of the most abundant carotenoids from edible brown seaweeds, for years has been used as a bioactive dietary supplement and functional food ingredient. Recently, fucoxanthin was reported to penetrate the blood-brain barrier, and was superior to other carotenoids to exert anti-neurodegenerative disorder effects via acting on multiple targets, including amyloid protein aggregation, oxidative stress, neuroinflammation, neuronal loss, neurotransmission dysregulation and gut microbiota disorder. However, the concentration of fucoxanthin required for in vivo neuroprotective effects is somewhat high, and the poor bioavailability of this molecule might prevent its clinical use. As such, new strategies have been introduced to overcome these obstacles, and may help to develop fucoxanthin as a novel lead for neurodegenerative disorders. Moreover, it has been shown that some metabolites of fucoxanthin may produce potent in vivo neuroprotective effects. Altogether, these studies suggest the possibility for future development of fucoxanthin as a one-compound-multiple-target or pro-drug type pharmaceutical or nutraceutical treatment for neurodegenerative disorders.Trial registration: ClinicalTrials.gov identifier: NCT03625284.Trial registration: ClinicalTrials.gov identifier: NCT02875392.Trial registration: ClinicalTrials.gov identifier: NCT03613740.Trial registration: ClinicalTrials.gov identifier: NCT04761406.

Network pharmacology-based approach to understand the effect and mechanism of Danshen against anemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen, the dried rhizome of Salvia miltiorrhiza Bge., is widely used to treat cardio-cerebrovascular diseases in China. However, its role in nourishing blood, which has been detailed in historical literature for thousands of years, is perpetually disputed in the academic field. Moreover, there is no systematic research on Danshen in treating anemia. This research aimed to investigate the effects and mechanisms of Danshen on anemia in a zebrafish model based on the results of a network pharmacology study. MATERIALS AND METHODS: The network pharmacology study was based on the screening of chemical components and related targets from TCMSP and SwissADME database. The genes associated with anemia were obtained from DisgeNet database, and the genes with the intersection of Danshen target genes were screened out. The Cytoscape 3.7.2 software package was used to construct the "ingredient-target-pathway" network. The exploration of target interaction by String system and the enrichment analysis by Metascape system, was used to discover the possible anti-anemia action mechanism of Danshen. Then, a zebrafish anemia model was induced by vinorelbine followed by the administration of aqueous/ethanol extract of Danshen in contrast to SiWu Decoction (SWD), which is generally acknowledged as a positive drug for tonifying blood. Afterward, the red blood cell signal, cardiac output, and blood flow velocity were detected to evaluate their blood-enriching effects. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the mRNA levels of hematopoietic-related factors, which were predicted in network pharmacology. RESULTS: Compounds and target screening hinted that 115 chemical targets from Danshen were related to anemia, KEGG pathway enrichment results suggested that the mechanism of Danshen in treating anemia was significantly related to the Jak-STAT signaling pathway. Pharmacodynamic results showed that aqueous extract of Danshen (DSAE) and ethanol extract of Danshen (DSEE) markedly enhanced the number of red blood cells, cardiac output, and blood flow velocity. Compared with DSAE, DSEE exerted anti-anemia effects at a lower dose; however, along with higher toxicity. PCR data demonstrated that DSAE and DSEE treatment both upregulated the mRNA expression of erythroid hematopoiesis-related factors in the Epo-JAK-STAT signaling pathway, such as Gata-1, Epo, EpoR, Jak2, STAT3, and STAT5. In general, DSAE exhibited higher activation of this signaling than DSEE. CONCLUSIONS: These results indicated that DSAE and DSEE both possess blood-enriching functions related with their ability to promote Jak-STAT signaling. DSAE exerted lower toxicity and attenuated anemia over a wider dose range than DSEE, which suggests that DSAE may be more suitable for the treatment for anemia. These results presented experimental evidence for the clinical use of Danshen as an intervention for anemia, especially in chemotherapy-induced anemia.

A new antibacterial chromone from a marine sponge-associated fungus Aspergillus sp. LS57.

Chemical investigation for the secondary metabolite of marine-derived fungus Aspergillus sp. LS57 resulted in the isolation of one new chromone named aspergilluone A (1) containing a chromone skeleton fused with an unusual hydrogenation cyclopentanoid ring, along with three known compounds 2-4. The structure of 1 was elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric analyses. Its absolute configuration was established by combining NMR quantum chemical calculations and comparison between the experimental and calculated circular dichroism (CD) curves. Additionally, the antibacterial assay of compound 1 was performed. As a result, compound 1 showed in vitro anti-Mycobacterium tuberculosis with MIC value of 32 µg/mL, together with moderate antibacterial activity against Staphylococcus aureus (MIC values = 64 µg/mL), and exhibited feeble activity against gram-positive Bacillus subtilis and gram-negative pathogen Escherichia coli (both MICs = 128 µg/mL).