Curative effect of the total saponins of Panax japonicus (TSPJ) on type 2 diabetes: Focusing on VEGFA.

OBJECTIVE: The objective of this study was to assess the impact of the total saponins of Panax japonicus (TSPJ) on Type 2 diabetes mellitus (T2DM). RESULTS: The intervention of TSPJ was found to have the ability to reverse physiological indicators associated with T2DM, while also enhancing the expression of genes involved in glucose metabolism and intestinal homeostasis. Additionally, alterations in the composition of the gut microbiota were observed. Based on the findings of experimental results and network pharmacology analysis, it is evident that vascular endothelial growth factor A (VEGFA) serves as a prominent shared target between TSPJ and diabetes. The outcomes observed in T2DM mice overexpressing VEGFA align with those observed in T2DM mice treated with TSPJ. CONCLUSIONS: TSPJ administration and VEGFA overexpression yield similar effects on T2DM in mice. Thus, in terms of mechanism, by upregulating the expression of VEGFA, TSPJ may ameliorate metabolic imbalance, preserve intestinal homeostasis, and lessen the symptoms of type 2 diabetes. The findings demonstrated the viability of using VEGFA as a type 2 diabetes therapy option and offered important insights into the therapeutic mechanisms by TSPJ in the management of T2DM. To determine the exact mechanisms behind the effects of TSPJ and VEGFA and to assess their potential therapeutic uses, more research efforts are necessary.

Melatonin enhances the developmental potential of immature oocytes from older reproductive-aged women by improving mitochondrial function.

Aims: To evaluate whether melatonin (MT) supplementation during in vitro maturation (IVM) of human oocytes can reverse the age-related decline in oocyte quality. Main methods: We enrolled 172 patients aged ≥35 years (older reproductive-aged women) and 83 patients aged <35 years (young women) who underwent in vitro fertilization between 2019 and 2022. We conducted IVM with and without 10 µM MT in immature oocytes of different ages. Oocyte fertilization and embryo development were observed using a stereomicroscope. We assessed the immunofluorescence intensity of mitochondrial function, measured the copy number of mitochondrial DNA (mtDNA), and examined the spindle and chromosome composition in in vitro mature stage II (IVM-MII) oocytes using immunofluorescence and second-generation sequencing. Key findings: MT supplementation significantly improved the redox level in the IVM medium and IVM-MII oocytes in older reproductive-aged women. It also significantly increased the proportion of circular mtDNA and the adenosine triphosphate content in IVM-MII oocytes. In addition, the IVM-MII oocytes obtained with MT supplementation showed a significant improvement in the normal composition of the spindle and chromosomes. Thus, the aged immature oocytes also showed significantly improved maturation and blastocyst formation rates owing to the role of MT. Significance: Supplementation with 10 µM MT in the IVM medium reverses the age-related decline in oocyte quality. Our findings provide a viable solution for enhancing fertility in older reproductive-aged women.

Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Moxibustion alleviates depression-like behavior in rats with Crohn's disease by inhibiting the kynurenine pathway metabolism in the gut-brain axis.

Background: Moxibustion is a potential therapy for inflammatory bowel disease-related depression, but its specific mechanism of action is unclear. This study aimed to investigate the molecular mechanism by which moxibustion alleviates depressive behavior in rats with Crohn's disease (CD). Methods: The CD rat model was established with 2,4,6-trinitrobenzenesulfonic acid. Treatment with moxibustion was applied to Tianshu (ST25, bilateral), Qihai (CV6), and Baihui (GV20) acupoints, and the effect of moxibustion was compared with that of the combination of moxibustion plus indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, 1-methyltryptophan (1-MT). The effects of moxibustion and moxibustion plus 1-MT combination on colonic inflammation and depressive behavior (assessed by forced swimming test, sucrose preference test, and open field test) were investigated. The changes in IDO1, TNF-α, and IL-1ß in rat colon and hippocampus were assessed by Western blot (WB). Gas chromatography-mass spectrometry, immunofluorescence staining, and WB were applied to detect kynurenine pathway (KP) metabolites, hippocampal neuronal activity, and microglia activation, respectively. Results: Both moxibustion and moxibustion plus 1-MT combination significantly alleviated intestinal inflammation and depressive behavior, downregulated the levels of IDO1 in the colon and hippocampus, and inhibited inflammation-inducing factors IL-1ß and TNF-α, as well as the kynurenine/tryptophan (KYN/TRP) ratio of KP metabolites, and upregulated the kynurenic acid (KYNA)/KYN ratio and the KYNA/quinolinic acid (QUIN) ratio in the hippocampus in rats with CD; Hippocampal ionized calcium-binding adaptor molecule-1 (Iba-1), c-fos protein expression, activated microglia, and neuronal activation was also significantly reduced by moxibustion and moxibustion plus 1-MT. The addition of 1-MT did not significantly increase the therapeutic effect of moxibustion. Conclusion: Moxibustion can improve depressive behavior in rats with CD, which may be related to its regulation of KP metabolism in the gut-brain axis and inhibition of hippocampal microglia activation and neuronal activation.

The Traditional Mongolian Medicine Qiqirigan-8 Effects on Lipid Metabolism and Inflammation in Obesity: Pharmacodynamic Evaluation and Relevant Metabolites.

Objective: Traditional Mongolian Medicine Qiqirigan-8 (MMQ-8) is a Chinese botanical drug with effective pharmacological properties in obesity. However, the pharmacological mechanism of MMQ-8 remains unclear. This study aimed to determine the active metabolites of MMQ-8 and its therapeutic effects on lipid metabolism and inflammation. Methods: The active metabolites of MMQ-8 were identified by ultrahigh-performance liquid chromatograph Q extractive mass spectrometry (UHPLC-QE-MS) assay and network analysis. An obesity rat model induced by high-fat diet was used in the study. Serum levels of lipids and inflammatory factors were detected using biochemical analysis and enzyme-linked immunosorbent assay (ELISA). Pathological analysis of liver tissues and arteries was conducted with hematoxylin and eosin (H&E) staining and immunohistochemistry. Protein expression of the tumor necrosis factor (TNF) signaling pathway was investigated by Western-blot. Simultaneously, bone marrow cells were used for RNA sequencing and relevant results were validated by cell culture and quantitative real-time polymerase chain reaction (RT-qPCR). Results: We identified 69 active metabolites and 551 target genes of MMQ-8. Of these, there are 65 active metabolites and 225 target genes closely related to obesity and inflammation. In vivo, we observed that MMQ-8 had general decreasing effects on body weight, white adipose tissue weight, and serum lipids. MMQ-8 treatment notably decreased the liver function markers and hepatic steatosis, and significantly decreased inflammation. In serum, it notably decreased TNF-α, interleukin (IL)-6, and inducible nitric oxide synthase (INOS), while elevating IL-10 levels. MMQ-8 treatment also significantly inhibited proteins phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα), mitogen-activated protein kinase (p38), extracellular regulated kinase 1/2(ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and decreased vascular endothelium damage and macrophage infiltration and polarization to M1. These findings coincide with the RNA-sequencing data of bone marrow cells and results of in vitro experiments. Conclusion: We determined the pharmacological actions and relevant metabolites of MMQ-8 in obesity for the first time. Our study revealed MMQ-8 can optimize lipid metabolism and reduce chronic inflammation in obesity. However, more in-depth research is needed, for example, to understand the principle of compound compatibility and the inhibition effects on hepatic steatosis, T cell differentiation, and inflammatory signal transduction.

A Comprehensive Identification and Expression Analysis of VQ Motif-Containing Proteins in Sugarcane (Saccharum spontaneum L.) under Phytohormone Treatment and Cold Stress.

The VQ motif-containing proteins play a vital role in various processes such as growth, resistance to biotic and abiotic stresses and development. However, there is currently no report on the VQ genes in sugarcane (Saccharum spp.). Herein, 78 VQ genes in Saccharum spontaneum were identified and classified into nine subgroups (I-IX) by comparative genomic analyses. Each subgroup had a similar structural and conservative motif. These VQ genes expanded mainly through whole-genome segmental duplication. The cis-regulatory elements (CREs) of the VQ genes were widely involved in stress responses, phytohormone responses and physiological regulation. The RNA-seq data showed that SsVQ gene expression patterns in 10 different samples, including different developmental stages, revealed distinct temporal and spatial patterns. A total of 23 SsVQ genes were expressed in all tissues, whereas 13 SsVQ genes were not expressed in any tissues. Sequence Read Archive (SRA) data showed that the majority of SsVQs responded to cold and drought stress. In addition, quantitative real-time PCR analysis showed that the SsVQs were variously expressed under salicylic acid (SA), jasmonic acid (JA), abscisic acid (ABA) and cold treatment. This study conducted a full-scale analysis of the VQ gene family in sugarcane, which could be beneficial for the functional characterization of sugarcane VQ genes and provide candidate genes for molecular resistance breeding in cultivated sugarcane in the future.

Multilayer control of cardiac electrophysiology by microRNAs.

The electrophysiological properties of the heart include cardiac automaticity, excitation (i.e., depolarization and repolarization of action potential) of individual cardiomyocytes, and highly coordinated electrical propagation through the whole heart. An abnormality in any of these properties can cause arrhythmias. MicroRNAs (miRs) have been recognized as essential regulators of gene expression through the conventional RNA interference (RNAi) mechanism and are involved in a variety of biological events. Recent evidence has demonstrated that miRs regulate the electrophysiology of the heart through fine regulation by the conventional RNAi mechanism of the expression of ion channels, transporters, intracellular Ca2+-handling proteins, and other relevant factors. Recently, a direct interaction between miRs and ion channels has also been reported in the heart, revealing a biophysical modulation by miRs of cardiac electrophysiology. These advanced discoveries suggest that miR controls cardiac electrophysiology through two distinct mechanisms: immediate action through biophysical modulation and long-term conventional RNAi regulation. Here, we review the recent research progress and summarize the current understanding of how miR manipulates the function of ion channels to maintain the homeostasis of cardiac electrophysiology.

Phytochrome interacting factor 3 regulates pollen mitotic division through auxin signalling and sugar metabolism pathways in tomato.

The development of viable pollen determines male fertility, and is crucial for reproduction in flowering plants. Phytochrome interacting factor 3 (PIF3) acts as a central regulator of plant growth and development, but its relationship with pollen development has not been determined. Through genetic, histological and transcriptomic analyses, we identified an essential role for SlPIF3 in regulating tomato (Solanum lycopersicum) pollen development. Knocking out SlPIF3 using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 resulted in pollen mitosis I arrest, and a failure to form viable pollen. We further demonstrated that both glutamate synthase 1 (SlGLT1) and cell wall invertase 9 (SlCWIN9), involved in auxin and sugar homeostasis, respectively, colocalised with SlPIF3 in the anthers and were directly regulated by SlPIF3. Knockout of either SlGLT1 or SlCWIN9 phenocopied the pollen phenotype of SlPIF3 knockout (Slpif3) lines. Slpif3 fertility was partially restored by exogenous auxin indole-3-acetic acid in a dose-dependent manner. This study reveals a mechanism by which SlPIF3 regulates pollen development and highlights a new strategy for creating hormone-regulated genic male sterile lines for tomato hybrid seed production.

Microbes: a potential tool for selenium biofortification.

Selenium (Se) is a component of many enzymes and indispensable for human health due to its characteristics of reducing oxidative stress and enhancing immunity. Human beings take Se mainly from Se-containing crops. Taking measures to biofortify crops with Se may lead to improved public health. Se accumulation in plants mainly depends on the content and bioavailability of Se in soil. Beneficial microbes may change the chemical form and bioavailability of Se. This review highlights the potential role of microbes in promoting Se uptake and accumulation in crops and the related mechanisms. The potential approaches of microbial enhancement of Se biofortification can be summarized in the following four aspects: (1) microbes alter soil properties and impact the redox chemistry of Se to improve the bioavailability of Se in soil; (2) beneficial microbes regulate root morphology and stimulate the development of plants through the release of certain secretions, facilitating Se uptake in plants; (3) microbes upregulate the expression of certain genes and proteins that are related to Se metabolism in plants; and (4) the inoculation of microbes give rise to the generation of certain metabolites in plants contributing to Se absorption. Considering the ecological safety and economic feasibility, microbial enhancement is a potential tool for Se biofortification. For further study, the recombination and establishment of synthesis microbes is of potential benefit in Se-enrichment agriculture.

Acupuncture for persistent atrial fibrillation after catheter ablation: study protocol for a pilot randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA). METHODS AND DESIGN: This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3 months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded. DISCUSSION: This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030576 . Registered on 7 March 2020.

Ammonia capture from human urine to harvest liquid N-P compound fertilizer by a submerged hollow fiber membrane contactor: Performance and fertilizer analysis.

In this study, we developed a submerged hollow fiber membrane contactor (HFMC) to recover ammonia from human urine to get compound N-P fertilizers. The ammonia capture performance, water vapor transmembrane performance, ion rejection performance and the liquid fertilizer components using 1-4 mol/L H3PO4 as the stripping solution was comprehensively investigated. Increasing H3PO4 concentration did not significantly affect the ammonia capture performance but the water vapor transfer and fertilizer components. The ammonia mass transfer coefficients were in a range of 1.95×10-6±4.77×10-8 to 2.28×10-6±6.71×10-8 m/s and the ammonia flux fluctuated between 17.80 and 20.80 g/m2·h. The water vapor flux increased with the increase of stripping solution concentration and the time elapsed. The N content (21.29-55.24 g/L) was in the range of the commercial products while the P2O5 content (99.41-281 g/L) was slightly higher, which can be used in the soils or plants with a high demand for phosphorus. The liquid fertilizers were all mixtures of (NH4)2HPO4 and NH4H2PO4, but the distribution ratio slightly changed with the different initial H3PO4 concentration. The economic assessment showed that harvesting liquid N-P fertilizer from human urine using HFMC can make a profit of $7.089/L.

Black phosphorus nanosheets and docetaxel micelles co-incorporated thermoreversible hydrogel for combination chemo-photodynamic therapy.

The platform of the combination chemo-photodynamic therapy has received widespread attention for enhancing anticancer efficacy and inhibiting tumor growth, which supports thermosensitive and controlled drug release. Here, an injectable thermoreversible hydrogel (BPNSs/DTX-M-hydrogel) co-encapsulating black phosphorus nanosheets (BPNSs) and docetaxel (DTX) micelles was prepared to increase drug accumulation in tumor tissue and improve anticancer efficacy. BPNSs were prepared by liquid exfoliation method with a simple and rapid preparation, and DTX micelles were prepared by the thin film dispersion method. Hydrogel was prepared with F127 as hydrogel matrix for intratumoral injection. BPNSs, DTX micelles, and BPNSs/DTX-M-hydrogel were characterized by particle size, morphology, stability and degradation, phase transition feature, and photodynamic performance. And the in vivo anticancer efficacy was evaluated in 4T1 tumor-bearing Balb/c mice. The results showed that the particle size of DTX micelles and BPNSs were about 16 and 180 nm, respectively. The hydrogel with the transformation temperature at near body exhibited great photodynamic efficacy and good biodegradability. Moreover, BPNSs/DTX-M-hydrogel with the combination of chemotherapy and photodynamic therapy exhibited unique anticancer efficacy with low toxicity. In conclusion, the combination platform of chemo-photodynamic therapy based on BPNSs could be a prospective strategy in antitumor research. Graphical abstract.

Enhancement and improvement of selenium in soil to the resistance of rape stem against Sclerotinia sclerotiorum and the inhibition of dissolved organic matter derived from rape straw on mycelium.

Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum (S. sclerotiorum), one of the most destructive diseases in many crops including Brassica napus L. The extensive use of fungicides to control S. sclerotiorum caused severe damage to the environment in the long term. Increasing study reported that selenium (Se) is a beneficial element for plant by promoting growth and enhancing disease resistance. In this study, it was found that Se in soil shortened lesion length by 19.14% on rape stem infected with S. sclerotiorum. While resistance mechanism of rape stem against S. sclerotiorum remains unknown. Transcriptomic analysis of rape stem was performed and the results indicated that genes related to antifungal pathways were up-regulated. Moreover, metabonomic analysis was carried out to study the inhibitive effect of the dissolved organic matter derived from rape straw with Se pretreatment in soil (RSDOMSe) on S. sclerotiorum mycelium, results showed that RSDOMSe caused severe damage to energy metabolism of mycelium. Further study indicated that RSDOMSe decreased the pathogenicity of mycelium on rape leaves significantly, and enhanced content of chlorophyII, carotenoids, OD phenol and activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) in rape leaves, which suggested that RSDOMSe plays a positive role in regulating oxidative stress responses of plant when infected with S. sclerotiorum. In addition, when compared with dimcthachlon (DIM) treatment alone, DIM combined with RSDOMSe resulted in higher inhibition on mycelial growth of S. sclerotiorum (the inhibition ratio of nearly 60%). Results in this study suggested that Se enhanced the resistance of rape stem against S. sclerotiorum because of the up-regulated genes related to antifungal pathways, and RSDOMSe improved the mycelial growth inhibition and decreased the pathogenicity of mycelium on rape leaves. Overall, Se as well as Se-enrich byproducts, possessed great potential to be developed as ecological fungicides for controlling S. sclerotiorum.

[Clinical efficacy of acupuncture combined with modified Xiangfu Decoction in treatment of menopausal insomnia cause by liver Qi stagnation].

To evaluate the efficacy and safety of acupuncture combined with modified Xiangfu Decoction in the treatment of menopausal insomnia case by liver Qi stagnation. Totally 120 cases were randomly divided into the control group(60 cases) and the treatment group(60 cases). Estazolam and acupuncture combined with modified Xiangfu Decoction were given for 16 weeks. Before and after treatment, Epworth sleepiness scale(ESS), Pittsburgh sleep quality index(PSQI), Hamilton anxiety scale(HAMA) and traditional Chinese medicine(TCM) syndrome score were compared between the two groups. Polysomnography monitor was used to monitor sleep progress and sleep structure. Serum LH, FSH and E_2 were determined. The clinical efficacy and incidence of adverse reactions were observed. Four cases were lost during the study. The total effective rate in the treatment group was 91.5%, which was higher than that in the control group 75.4%(P<0.05). After treatment, the scores of clinical symptoms(ESS, PSQI, HAMA, TCM symptoms) in the treatment group were significantly reduced(P<0.05), and lower than that in the control group(P<0.05). TST, SE in the treatment group were increased(P<0.05), while AWT, SL, AT in the treatment group were decreased(P<0.05), and the improvement was more significant than that in the control group(P<0.05). S_1 in the treatment group was decreased(P<0.05), whereas S_2, S_(3+4), REM in the treatment group were increased(P<0.05), and the improvement was more significant than that in the control group(P<0.05). The contents of LH and FSH in the treatment group were significantly reduced(P<0.05), while the content of E_2 was significantly increased(P<0.05), and the changes were more significant than those in the control group(P<0.05). The incidence of adverse reactions in the control group was 8.8%, which was higher than 1.7% in the treatment group(P<0.05). Acupuncture combined with modified Xiangfu Decoction could significantly improve the sleep status of menopausal insomnia cases caused by liver Qi stagnation, with a lower incidence of adverse reactions, and so is worthy of clinical promotion and application.

Selenium reduces the pathogenicity of Sclerotinia sclerotiorum by inhibiting sclerotial formation and germination.

Sclerotinia sclerotiorum (S. sclerotiorum) is a devastating fungal pathogen with worldwide distribution, and threatened the agro-ecological safety in the long term. To control the damage caused by Sclerotinia diseases, as well as consider the fungicide resistance and chemical residues, strategy of which plant nutritional regulation, as an eco-friendly approach, is gaining much significance. Selenium (Se), as a beneficial microelement for plant, has been manifested to be effective in inhibiting the mycelial growth of S.sclerotiorum in our previous study. In the present study, we observed that Se (both selenate and selenite) inhibited the formation of sclerotia, which is an important life form in the disease cycle of S. sclerotiorum. And the inhibition ratios of number of sclerotia in treatments of Se(VI)5.0 and Se(IV)5.0 were 54.55% and 43.84%, respectively; the inhibition ratios of weight of sclerotia in treatments of Se(VI)5.0 and Se(IV)5.0 were 42.29% and 25.67%, respectively. Results suggested that Se inhibited mycelial growth, severely damaged sclerotial ultrastructure, reduced the capacity of acid production, decreased superoxide dismutase (SOD) and catalase (CAT) activities, increased the content of hydrogen peroxide (H2O2) and superoxide anion (O2-) in mycelium, and all of these resulted in the reduction in sclerotial formation. Further studies revealed that Se application in medium increased Se concentration in sclerotia and thus inhibited sclerotial germination. Moreover, the pathogenicity of mycelia germinating from sclerotia that pretreated with Se, decreased significantly to rape leaves. These findings broadened our understanding of Se application in plant protection, as well as provided evidences for developing environment-friendly fungicide for S. sclerotiorum control.

Black phosphorus nanosheets and gemcitabine encapsulated thermo-sensitive hydrogel for synergistic photothermal-chemotherapy.

The purpose of this study was to propose a thermosensitive hydrogel incorporating black phosphorus (BP) nanosheets and gemcitabine for chemo-photothermal combination therapy against cancer. The BP nanosheets were prepared by liquid exfoliation method and the thermo-sensitive hydrogel was prepared by "cold method" with Pluronic F127 as hydrogel matrix for intratumoral injection. BP nanosheets and the hydrogel were characterized by particle size, morphology, phase transition feature, near infrared photothermal conversion performance, photothermal stability and biodegradation. The in vitro release behaviors of gemcitabine were assessed. Moreover, the photothermal efficacy, and photothermal-chemotherapy combination were evaluated in mice bearing tumors. The BP nanosheets displayed uniform 2D sheet-like morphology with a diameter of about 200 nm. The hydrogel showed phase translation at near body temperature, great photothermal efficacy in vitro and good biodegradability. The hydrogel exhibited good photothermal effect in BALB/c mice bearing 4T1 xenograft tumors. The combination of photothermal therapy and chemotherapy displayed superior antitumor effect compared to chemotherapy alone.

pH/near infrared dual-triggered drug delivery system based black phosphorus nanosheets for targeted cancer chemo-photothermal therapy.

Recently, chemo-photothermal has been developed as a promising strategy for cancer therapy. However, as a novel photothermal material, black phosphorus nanosheet (BP NSs) has the disadvantages of complicated preparation procedures, high purchase price and poor drug selectivity, which limits its application. Herein, BP NSs have been successfully prepared by self-made ultrasonic method, which was a simple and rapid laboratory preparation. Then, BP NSs based co-delivery system, which coated with mitoxantrone hydrochloride (MTX) and hyaluronic acid (HA) on the surface of BP NSs has been firstly developed via electrostatic interaction. The resulted BP@MTX-HA NSs not only have good physical stability and photothermal conversion efficiency, but also exhibit the unique pH/NIR laser triggered release abilities. Besides, the temperature both in vitro and vivo could rise up to 45 °C or more within 3 min under 808 nm near infrared (NIR) irradiation (1.0 W/cm2). Additionally, through the antitumor phototherapy efficacy investigation in 4T1 tumor-bearing BALB/c mice, BP@MTX-HA NSs exhibited significant inhibition on tumor growth and obvious superiorities over the single treatment of MTX chemotherapy or NIR photothermal therapy in terms of chemo-photothermal synergistic treatment and targeted co-delivery system. In conclusion, pH/NIR dual-triggered drug delivery system based BP NSs would be a prospective strategy in the chemo-photothermal medical fields through our preliminary assessments.

An overview of fungal glycan-based therapeutics.

Edible medicinal mushrooms have been traditionally used for health promotion and longevity in China and other East Asian countries for centuries. Structural and pharmacological studies revealed that fungal glycans show multiple physiological and healthy promoting effects including immunomodulation, anti-tumor, anti-aging, anti-oxidation, hypoglycemic, hypolipidemic, anti-radiation, and other effects. Fungal glycans isolated from different kinds of medicinal mushrooms are partially purified and clinically tested. Without serious safety concerns of mostly glycans from edible mushrooms and/or the cultured mycelium, eight of them are approved by Chinese Food and Drug Administration (SFDA) and used clinically in China since 1980s. In this chapter, 185 independent studies involving in biochemical, pharmacological and clinical studies of fungal glycans during the past four decades (1977-2019) from PubMed, CNKI (China National Knowledge Infrastructure) and Wanfang databases are summarized. In future, understanding the fungal glycan-based drugs at molecular biological level would be needed to comprehend the clinical efficacy of glycan-based drugs.

Tomato stigma exsertion induced by high temperature is associated with the jasmonate signalling pathway.

High temperature (HT) is becoming an increasingly serious factor in limiting crop production with global climate change. During hot seasons, owing to prevailing HT, cultivated tomatoes are prone to exhibiting stigma exsertion, which hampers pollination and causes fruit set failure. However, the underlying regulatory mechanisms of the HT-induced stigma exsertion remain largely unknown. Here, we demonstrate that stigma exsertion induced by HT in cultivated tomato is caused by more seriously shortened stamens than pistils, which is different from the stigma exsertion observed in wild tomato species. Under the HT condition, the different responses of pectin, sugar, expansin, and cyclin cause cell wall remodelling and differentially localized cell division and selective cell enlargement, which further determine the lengths of stamens and pistils. In addition, auxin and jasmonate (JA) are implicated in regulating cell division and cell expansion in stamens and pistils, and exogenous JA instead of auxin treatment can effectively rescue tomato stigma exsertion through regulating the JA/COI1 signalling pathway. Our findings provide a better understanding of stigma exsertions under the HT condition in tomato and uncover a new function of JA in improving plant abiotic stress tolerance.

[Preparation and evaluation of gastric adhesive-floating pellets for Bolo leaf phenols].

Gastric adhesive-floating pellets for Bolo leaf phenols (BLP) were prepared by extrusion-spheronization method, with chitosan as skeleton bioadhesive material, and stearyl alcohol as help-bleaching agent to evaluate its in vitro adhesivity, floatability and in vivo retention situation, and investigate its in vitro release characteristics. The in vitro adhesivity and floatability were evaluated respectively by in vitro tissue retention method and visual observation method. The retention of pellets in rats was investigated by in vivo tissue retention method and in vivo imaging of small animals. In addition, the in vitro release of p-coumaric acid and caffeic acid as the index components in pellets were evaluated. Results showed that the in vitro adhesivity of the prepared gastric adhesive-floating pellets reached (73.2±3.4)%, and the pellets could float immediately in simulated gastric fluid for more than 12 h; the retention rate of adhesive-floating pellets in rats reached more than 40% after 6 h, while the retention rate of common reference pellets was decreased by 15% as compared with the gastric adhesive-floating pellets, with significant difference (P<0.01); the drug in vitro release time can reach more than 6 h, and the drug release behaviors were lined with Higuchi equation. In vivo and in vitro studies showed that, the gastrointestinal bioadhesive and floating pellets prepared in this study have good bioadhesivity, floatability and good sustained release characteristics.