Moxibustion preconditioning reduces inflammatory response in rats with cerebral ischemia-reperfusion injury by regulating PI3K / AKT / mTOR signaling pathway. / 艾灸预处理通过调控PI3K/AKT/mTORä¿¡å·é€šè·¯å‡è½»è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ ç‚Žæ€§ååº”.

OBJECTIVES: To observe the effect of moxibustion preconditioning on inflammatory response in rats with cerebral ischemia reperfusion injury (CIRI), so as to explore its mechanisms underlying improving CIRI. METHODS: Seventy-five male SD rats were randomly divided into sham operation, model, moxibustion preconditioning 3 days (Moxi 1), moxibustion preconditioning 5 days (Moxi 2) and moxibustion preconditioning 7 days (Moxi 3) groups, with 15 rats in each group. Moxibustion was applied at "Baihui"(GV20), "Dazhui"(GV14) and "Zusanli"(ST36) for 20 min once a day, totally for 3, 5 or 7 days. Thirty minutes after the last moxibustion treatment, the CIRI model was established by occlusion of the middle cerebral artery. The neurological deficit score was assessed by using Longa's method. The infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The morphological changes of cortical neurons were observed by HE staining. The contents of inflammatory factors interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), S-100ß protein (S-100ß) and neuron-specific enolase (NSE) were detected by ELISA. The expression of phosphatidylinositol-3-kinase (PI3K), p-PI3K, protein kinase B (AKT) and mammalian target of rapamycin (mTOR) proteins in the ischemic cortex tissues were detected by immunohistochemistry and Western blot. RESULTS: Compared with the sham operation group, the neurological function score and the percentage of cerebral ischemic volume were increased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly increased (P<0.01), while the protein expressions of PI3K, p-PI3K, AKT and mTOR in the cerebral cortex were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function score and the percentage of cerebral ischemic volume were significantly decreased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly decreased (P<0.01), and the expressions of PI3K, p-PI3K, AKT and mTOR proteins in the cerebral cortex were significantly increased (P<0.01) in three moxibustion groups. Compared with the Moxi 1 and Moxi 2 groups, the above indicators were significantly improved in rats of the Moxi 3 group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion preconditioning can significantly improve the neurological function of rats after ischemia-reperfusion, inhibit serum inflammatory factors IL-1 ß and TNF-α, inhibit brain tissue injury markers S-100ß and NSE, which may be related to the activation of PI3K/AKT/mTOR signaling pathway. The protective effect of moxibustion preconditioning for 7 days on CIRI was better than that of 5 days and 3 days.

Effects of Variation in Tamarix chinensis Plantations on Soil Microbial Community Composition in the Middle Yellow River Floodplain.

Floodplains have important ecological and hydrological functions in terrestrial ecosystems, experience severe soil erosion, and are vulnerable to losing soil fertility. Tamarix chinensis Lour. plantation is the main vegetation restoration measure for maintaining soil quality in floodplains. Soil microorganisms are essential for driving biogeochemical cycling processes. However, the effects of sampling location and shrub patch size on soil microbial community composition remain unclear. In this study, we characterized changes in microbial structure, as well as the factors driving them, in inside- and outside-canopy soils of three patch sizes (small, medium, large) of T. chinensis plants in the middle Yellow River floodplain. Compared with the outside-canopy soils, inside-canopy had higher microbial phospholipid fatty acids (PLFAs), including fungi, bacteria, Gram-positive bacteria (GP), Gram-negative bacteria (GN), and arbuscular mycorrhizal fungi. The ratio of fungi to bacteria and GP to GN gradually decreased as shrub patch size increased. Differences between inside-canopy and outside-canopy soils in soil nutrients (organic matter, total nitrogen, and available phosphorus) and soil salt content increased by 59.73%, 40.75%, 34.41%, and 110.08% from small to large shrub patch size. Changes in microbial community composition were mainly driven by variation in soil organic matter, which accounted for 61.90% of the variation in inside-canopy soils. Resource islands could alter microbial community structure, and this effect was stronger when shrub patch size was large. The results indicated that T. chinensis plantations enhanced the soil nutrient contents (organic matter, total nitrogen, and available phosphorus) and elevated soil microbial biomass and changed microbial community composition; T. chinensis plantations might thus provide a suitable approach for restoring degraded floodplain ecosystems.

A liposome-based aptasensor integrated with competitive reaction enabling portable and electrochemical detection of Aß oligomer.

Aggregation of ß-amyloid (Aß) were considered as a typical pathological feature of Alzheimer's disease (AD). Extensive studies have verified that soluble Aß oligomers (AßO) were more toxic to neurons than plaques. Herein, in this work, a glucose entrapped liposome-based portable aptasensor was fabricated for recognizing and interacting with AßO by specific aptamer on liposome (G-Lip-Apt). Then, a single strand DNA, designed to be partially complementary to AßO aptamer, was modified on amino-functionalized Fe3O4@SiO2 to obtain a magnetic nanocomposite (Fe3O4@SiO2/NH2-DNA). In the presence of AßO, the specific recognition between AßO and its aptamer on G-Lip-Apt made AßO bounded with G-Lip-Apt. With subsequent introduction of Fe3O4@SiO2/NH2-DNA, the unreacted G-Lip-Apt was further linked with Fe3O4@SiO2/NH2-DNA by double stranded complementary pairing interaction. Along with the addition of TritonX-100 into the formed G-Lip-Apt/Fe3O4@SiO2/NH2-DNA complex, the encapsulated glucose was released from liposome and then measured by a personal glucose meter (PGM). Good linear correlation was acquired over concentration of 5.0-1000 nM and the limit of detection (LOD) was calculated to be 2.27 nM for AßO. The developed portable electrochemical strategy integrated magnetic separation, competitive reaction and point of care test (POCT) to achieve high sensitivity, selectivity and accuracy, therefore enabled it successfully applied to the analysis of AßO in the hippocampus and cortex of APP/PS1 transgenic AD mice.

Holocene seasonal temperature evolution and spatial variability over the Northern Hemisphere landmass.

The origin of the temperature divergence between Holocene proxy reconstructions and model simulations remains controversial, but it possibly results from potential biases in the seasonality of reconstructions or in the climate sensitivity of models. Here we present an extensive dataset of Holocene seasonal temperatures reconstructed using 1310 pollen records covering the Northern Hemisphere landmass. Our results indicate that both summer and winter temperatures warmed from the early to mid-Holocene (~11-7 ka BP) and then cooled thereafter, but with significant spatial variability. Strong early Holocene warming trend occurred mainly in Europe, eastern North America and northern Asia, which can be generally captured by model simulations and is likely associated with the retreat of continental ice sheets. The subsequent cooling trend is pervasively recorded except for northern Asia and southeastern North America, which may reflect the cross-seasonal impact of the decreasing summer insolation through climatic feedbacks, but the cooling in winter season is not well reproduced by climate models. Our results challenge the proposal that seasonal biases in proxies are the main origin of model-data discrepancies and highlight the critical impact of insolation and associated feedbacks on temperature changes, which warrant closer attention in future climate modelling.

Effects of Bu Shen Hua Zhuo formula on the LPS/TLR4 pathway and gut microbiota in rats with letrozole-induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in gynecology. Traditional Chinese medicine (TCM) is widely used for the treatment of PCOS in China. The Bu Shen Hua Zhuo formula (BSHZF), a TCM decoction, has shown great therapeutic efficacy in clinical practice. However, the mechanism underlying the BSHZF function in PCOS remains unclear. This study aimed to identify the potential mechanisms of action of BSHZF in the treatment of PCOS. PCOS-model rats treated with letrozole were administered different doses of BSHZF, metformin, and 1% carboxymethylcellulose. Serum sex hormones, fasting blood glucose, and fasting insulin levels were measured, and the morphology of the ovaries was observed in each group, including the normal group. The structure and abundance of the gut microbiota in rats were measured using 16S ribosomal RNA gene sequencing. Toll-like receptor 4 (TLR4) and phospho-NF-κB p65 levels in the ovarian tissue of the rats were detected using Western blotting. Furthermore, the levels of lipopolysaccharide (LPS) and inflammatory cytokines TNF-α, IL-6, and IL-8 in the serum of rats were detected by ELISA. The results showed that BSHZF administration was associated with a decrease in body weight, fasting blood glucose, fasting insulin, and testosterone and changes in ovarian morphology in PCOS-model rats. Moreover, BSHZF was associated with an increase in the α-diversity of gut microbiota, decrease in the relative abundance of Firmicutes, and increase in Lactobacillus and short chain fatty acid-producing bacteria (Allobaculum, Bacteroides, Ruminococcaceae_UCG-014). Furthermore, BSHZF may promote carbohydrate and protein metabolism. In addition, BSHZF was associated with a decrease in the serum level of LPS and TLR4 expression, thereby inhibiting the activation of the NF-κB signaling-mediated inflammatory response in ovarian tissue. Therefore, the beneficial effects of BSHZF on PCOS pathogenesis are associated with its ability to normalize gut microbiota function and inhibit PCOS-related inflammation.

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B.

Background: Polyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury. Methods: This study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated. Results: The final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: -3.7, 95% CI, -6.0 to -1.5 U/L/day; -2.4, 95% CI, -4.5 to -0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (-5.2, 95% CI, -5.8 to -4.5 U/L/day; -3.5, 95% CI, -4.2 to -2.7 U/L/day; -4.9, 95% CI, -6.2 to -3.7 U/L/day, -0.07, 95% CI, -0.09 to -0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (-2.6, 95% CI, -3.3 to -1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (-1.4, 95% CI, -2.4 to -0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC. Conclusion: This was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

Multifunctional Metal-Organic Framework as a Versatile Nanoplatform for Aß Oligomer Imaging and Chemo-Photothermal Treatment in Living Cells.

In view of the close association of ß-amyloid oligomers (AßO) with the clinical development of Alzheimer's disease (AD) symptoms, it is urgent to design a promising sensing and therapeutic strategy that can target AßO for preventing or delaying the onset of AD. Herein, a core-shell nanocomposite CeONP-Res-PCM@ZIF-8/polydopamine (PDA) was synthesized through an in situ encapsulated strategy, in which resveratrol (Res), ceria nanoparticles (CeONPs), and PCM (tetradecanol) were embedded into the ZIF-8/PDA matrix via a water-based mild approach. Using the AßO aptamer, the ability of CeONP-Res-PCM@ZIF-8/PDA/Apt as the fluorescent sensing platform for AßO detection and intracellular imaging was demonstrated. The nanocomposite was high in Res loading (27.5%) and could be activated to release the encapsulated Res upon illumination with NIR through PCM regulation. Moreover, due to the synergetic interactions of PDA, CeONPs, and Res in one system, CeONP-Res-PCM@ZIF-8/PDA/Apt nanocomposites exhibited multifunctional effects on inhibiting Aß aggregation, degrading Aß fibrils, and alleviating Aß-induced oxidative stress and neural apoptosis. These therapeutic effects could be enhanced under NIR irradiation by virtue of the excellent photothermal property of PDA. As far as we know, there is no report of using ZIF-8-based materials for simultaneous sensing and therapeutic applications. This work boosted the development of multifunctional nanoagents for biomedical research studies.

ß-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota.

Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of ß-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota. Methods: The presence of ß-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of ß-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανß3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing. Results: With the treatment of ß-sitosterol and ß-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανß3, LIF, HOXA10, FSH, and P increased. Under ß-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed. Conclusion: ß-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.

Determination of the antidiabetic chemical basis of Phellodendri Chinensis Cortex by integrating hepatic disposition in vivo and hepatic gluconeogenese inhibition in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Phellodendri Chinensis Cortex (PCC) has been an herb clinically used to treat diabetes, but the chemical basis of its antidiabetic effects has remained unclear. AIM OF THIS STUDY: Based on the efficacy of herbal medicine resulting from the cooperative response of the effective compounds in the target organs with sufficient exposure, the in vivo hepatic disposition and in vitro hepatic gluconeogenesis inhibition were integrated to elucidate the chemical basis for the antidiabetic effect of orally administered PCC from a target organ, liver, perspective. MATERIALS AND METHODS: With a developed and validated HPLC-MS/MS method, three alkaloids and five metabolites were determined in the portal vein plasma, liver, and systemic plasma of rats orally administered PCC. The inhibition of hepatic gluconeogenesis by the eight compounds was evaluated in primary hepatocytes. RESULTS: The in vivo results showed that magnoflorine was present at the highest concentration among the target constituents in the plasma, where berberine showed a low concentration. In contrast, berberine showed the highest concentration in the liver, and its five metabolites exhibited substantial hepatic accumulation. This discrepancy was strongly associated with the hepatic disposition of the compounds. The hepatic disposition prevented the transfer of 96.1% of the phellodendrine, 71.1% of the berberine and 47.5% of the magnoflorine from the portal vein plasma to the systemic plasma, which corresponded to their hepatic distribution and hepatic metabolism. In vitro, berberine, M1, M4 and M5 significantly and dose-dependently inhibited hepatic glucose production. By integrating the hepatic exposure and inhibitory activity data, we estimated that berberine contributed the most (74%) to the total glucose production inhibition of the orally administered PCC decoction, followed by M4 (14%), M1 (11%) and M5 (1%). CONCLUSION: This study was the first to comprehensively describe the pharmacokinetic profiles and hepatic disposition of alkaloids in PCC, and concluded that berberine and its metabolites contributed the most to the total hepatic gluconeogenesis inhibition by orally administered PCC. These results reveal the chemical basis for the antidiabetic effect of orally administered PCC decoction, providing scientific evidence to support the clinical usage of PCC in diabetes treatment.

Letrozole and the Traditional Chinese Medicine, Shaofu Zhuyu Decoction, Reduce Endometriotic Disease Progression in Rats: A Potential Role for Gut Microbiota.

We previously showed that the Chinese herbal medicine, Shaofu Zhuyu decoction (SFZYD), shrank the size of endometriotic lesions in rats with endometriosis. We therefore conducted the present study to investigate the effects of letrozole and SFZYD on gut microbiota in endometriotic rats. Rats were divided into four groups: a blank group, model group, letrozole group, and SFZY group. Ectopic lesion size and COX-2 expression in the endometrium and endometriotic lesions were compared, and the community of gut microbiota was detected using 16S rRNA gene sequencing. Both letrozole and SFZYD reduced the size of ectopic lesions as well as lowered the expression of COX-2, thus reducing the inflammatory response. Compared with the blank group, the α-diversity of gut microbiota in endometriotic rats decreased, the Firmicutes/Bacteroidetes ratio increased, and the abundance of Ruminococcaceae was reduced. The α-diversity of gut microbiota in the letrozole group was similar to that in the model group, but the Firmicutes/Bacteroidetes ratio was diminished. The α-diversity in the SFZY group was similar to that in the blank group, the Firmicutes/Bacteroidetes ratio was attenuated, and the abundance of Ruminococcaceae was elevated compared with the model group. These results indicated that the therapeutic mechanisms of both letrozole and SFZYD were related to the restoration of gut microbiota.

Facile Construction of i-Motif DNA-Conjugated Gold Nanostars as Near-Infrared and pH Dual-Responsive Targeted Drug Delivery Systems for Combined Cancer Therapy.

Stimuli-responsive DNA-based nanostructures have emerged as promising vehicles for intelligent drug delivery. In this study, i-motif DNA-conjugated gold nanostars (GNSs) were fabricated in a facile manner as stimuli-responsive drug delivery systems (denoted as A-GNS/DNA/DOX) for the treatment of cancer via combined chemo-photothermal therapy. The i-motif DNA is sensitive to the environmental pH and can switch from a single-stranded structure to a C-tetrad (i-motif) structure as the environmental pH decreases from neutral (∼7.4) to acidic (<6.0). The loaded drug can then be released along with the conformational changes. To enhance cellular uptake and improve cancer cell selectivity, the aptamer AS1411, which recognizes nucleolins, was employed as a targeting moiety. The A-GNS/DNA/DOX nanocomposites were found to be highly capable of photothermal conversion and exhibited photostability under near-infrared (NIR) irradiation, and the pH and NIR irradiation effectively triggered the drug-release behaviors. In addition, the A-GNS/DNA/DOX nanocomposites exhibited good biocompatibility. The targeting recognition enabled the A-GNS/DNA/DOX to exhibit higher cellular uptake and therapeutic efficiency than the GNS/DNA/DOX. Notably, under NIR irradiation, a synergistic effect between chemotherapy and photothermal therapy can be achieved with the proposed delivery system, which exhibits much higher therapeutic efficiency both in monolayer cancer cells and tumor spheroids as compared with a single therapeutic method. This study highlights the potential of GNS/DNA nanoassemblies for intelligent anticancer drug delivery and combined cancer therapy.

Gold Cube-in-Cube Based Oxygen Nanogenerator: A Theranostic Nanoplatform for Modulating Tumor Microenvironment for Precise Chemo-Phototherapy and Multimodal Imaging.

Engineering a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions has always been an intractable challenge in targeted cancer treatment. Herein, to actualize the theme of precise medicine, a nanoplatform is developed by anchoring Mn-Cdots to doxorubicin (DOX)-loaded mesoporous silica-coated gold cube-in-cubes core/shell nanocomposites and further conjugating them to a Arg-Gly-Asp (RGD) peptide (denoted as RGD-CCmMC/DOX) to achieve an active-targeting effect. Under 635 nm irradiation, the nanoplatform acts as oxygen nanogenerator that produces O2 in situ and amplifies the content of singlet oxygen (1O2) in the hypoxic tumor microenvironment (TME), which has been demonstrated to attenuate tumor hypoxia and synchronously enhance photodynamic efficacy. Moreover, the gold cube-in-cube core in this work has been proven as a photothermal agent for hyperthermia, which exhibits a favorable photothermal effect with a 65.6% calculated photothermal conversion efficiency under 808 nm irradiation. In addition, the nanoplatform achieves heat- and pH-sensitive drug release with precise control to specific-tumor sites, executing combined chemo-phototherapy functions. Besides, it functions as a multimodal bioimaging agent of photothermal, fluorescence, and magnetic resonance imaging for the accurate diagnosis and guidance of therapy. As validated by in vivo and in vitro assays, the TME-responsive nanoplatform is highly biocompatible and effectively obliterates 4T1 tumor xenografts on nude mice after triple-synergetic treatment. This work presents a rational design of versatile nanoplatforms, which modulate the TME to enable high therapeutic performance and multiplexed imaging, which provides an innovative paradigm for targeted tumor therapy.

Acute-onset multiple acyl-CoA dehydrogenase deficiency mimicking Guillain-Barré syndrome: two cases report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) showed great clinical heterogeneity and poses a challenge to diagnosis. Guillain-Barré syndrome (GBS) is an acute-onset autoimmune-mediated peripheral neuropathy. However, no patients of acute-onset MADD mimicking the GBS phenotype are reported previously. CASE PRESENTATION: Two patients displayed acute-onset limb weakness, areflexia, and length-dependent sensory disturbances, which clinically indicate the diagnosis of GBS, but electrophysiological and cerebrospinal fluid results threw doubtful points to the initial diagnosis. The muscle biopsy showed lipid storage disorder; and compound heterozygous mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene were found in the two patients through targeted next generation sequencing, which provided the definite diagnostic evidences of late-onset MADD. Muscle weakness was quickly improved by riboflavin supplementation, but sensory disturbances required a long-term treatment. DISCUSSION: The present two cases have demonstrated that MADD can mimic GBS. Taking into consideration the significant differences of therapeutic regimen and prognosis, MADD should be included in the differential diagnosis of GBS.

DNA-Stabilized Silver Nanoclusters for Label-Free Fluorescence Imaging of Cell Surface Glycans and Fluorescence Guided Photothermal Therapy.

A multifunctional nanoplatform that enables the integration of biological detection, imaging diagnosis, and synergistic therapy into a single nanostructure holds great promise for nanoscience and nanomedicine. Herein, a novel theranostic platform was presented for label-free imaging of cell surface glycans based on DNA/silver nanoclusters (AgNCs) via hybridization chain reaction (HCR) and fluorescence guided photothermal therapy (PTT). In this strategy, a dibenzocyclooctyne (DBCO)-functionalized DNA and two hairpin structures of DNA/AgNCs probes were involved. Following metabolic glycan labeling, the binding of DBCO-functionalized DNA to cell surface initiated HCR, and then cell surface glycans were specifically labeled by DNA/AgNCs fluorescent probes. Furthermore, this signal amplification strategy was adopted in quantitative analysis, and the detection limit could be achieved as low as 20 cells in 200 µL of binding buffer. Moreover, the remarkable photothermal properties of DNA/AgNCs via HCR led to efficient killing of cancer cells and inhibited the tumor growth under imaging guide. In this strategy, DNA/AgNCs were utilized to detect the cellular glycans, which aided in overcoming the high cost and instability of fluorescent dyes. Simultaneously, the HCR process avoided the introduction of excessive azido-sugars under the precondition of ensuring apparent fluorescence. These results indicated that the developed nanoplatform has great potential for specific cell surface glycans imaging and fluorescence guided PTT.

CSH guidelines for the diagnosis and treatment of drug-induced liver injury.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

Simulation Study of an Ultrasound Retinal Prosthesis With a Novel Contact-Lens Array for Noninvasive Retinal Stimulation.

Millions of people around the world suffer from varying degrees of vision loss (including complete blindness) because of retinal degenerative diseases. Artificial retinal prosthesis, which is usually based on electrical neurostimulation, is the most advanced technology for different types of retinal degeneration. However, this technology involves placing a device into the eyeball, and such a highly invasive procedure is inevitably highly risk and expensive. Ultrasound has been demonstrated to be a promising technology for noninvasive neurostimulation, making it possible to stimulate the retina and induce action potentials similar to those elicited by light stimulation. However, the technology of ultrasound retinal stimulation still requires considerable developments before it could be applied clinically. This paper proposes a novel contact-lens array transducer for use in an ultrasound retinal prosthesis (USRP). The transducer was designed in the shape of a contact lens so as to facilitate acoustic coupling with the eye liquid. The key parameters of the ultrasound transducer were simulated, and results are presented that indicate the achievement of 2-D pattern generation and that the proposed contact-lens array is suitable for multiple-focus neurostimulation, and can be used in a USRP.

LC-MS/MS method for the simultaneous quantification of 11 compounds of Ginkgo biloba extract in lysates of mesangial cell cultured by high glucose.

The mesangial cell (MC) cultured with high glucose has been used to observe the protective effect of Ginkgo biloba extract (GBE) against diabetic nephropathy (DN), but the compounds interacting with cell are still unknown, which may be potential bioactive components. Based on this, the determination of GBE in MC lysates was proposed by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) in this study. The MC was cultured with normal or high glucose with GBE for 4, 8, 12, 16, 24 and 48h. The harvested cell was extracted with 40% acetic acid in water and further analyzed by LC-MS/MS. All the validation data including linearity, intra-day and inter-day precision, limit of detection and quantification, matrix effect, and stability were within the required limits. The validated method was successfully applied to quantify 11 compounds of GBE in cell lysates. The results showed that high glucose prolonged the peak time of all observed 11 compounds and peak concentrations of bilobalide, ginkgolide C, ginkgolide B, quercetin, luteolin, kaempferol, isorhamnetin and genkwanin in cell lysates, which hinted that these compounds may be the potential bioactive components of GBE with preventive effect against DN.

Screening for Potential Bioactive Components in Ginkgo biloba Extract by the Rat Renal Tubular Epithelial Cell Extraction and LC-MS/MS.

Rat renal tubular epithelial cell (RTEC) cultured with high glucose has been used to observe the protective effect of Ginkgo biloba extract (GBE) against diabetic nephropathy (DN). The compounds in GBE binding with cell membrane or entering into cell are still unknown, which may be potential bioactive components. In this paper, a powerful method for screening and analyzing the potential bioactive components from GBE was developed using cell extraction coupled with high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). 8 prototype compounds and 5 metabolites were obtained, among which 6 prototype compounds and 1 metabolite were identified or tentatively characterized as rutin, bilobalide, ginkgolide B, ginkgolide C, genkwanin, apigenin and diosmetin by comparing their retention times and MS spectra with those of authentic standards or literature data. The 6 prototype compounds were further quantitatively analyzed using electrospray ionization in negative mode multiple reaction monitoring (MRM). The results showed that high glucose changed the Tmax, MRT(0-t), Cmax and AUC(0-t) of all observed compounds and decreased the t1/2 of genkwanin and apigenin, significantly. The overall findings indicate that 8 prototype compounds may be the potential bioactive components of GBE with preventive effect against DN and the method of RTEC extraction coupled with LC-MS/MS technology screening method we developed is a feasible, rapid, and useful tool for screening and analyzing potential bioactive components.

Target cell extraction coupled with LC-MS/MS analysis for screening potential bioactive components in Ginkgo biloba extract with preventive effect against diabetic nephropathy.

A rapid and useful approach for screening potential bioactive components in Ginkgo biloba extract (GBE) with preventive effect against diabetic nephropathy (DN) was developed using mesangial cells extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Mesangial cells were first divided into two groups according to their treatments with high glucose or high glucose plus GBE. After incubation for 4, 8, 12, 16, 24 and 48 h, the cells were harvested and extracted with 40% acetic acid in water before LC-MS/MS analysis. Then, 19 compounds and five metabolites were found to selectively combine with mesangial cells. Notably, compounds including quercetin and rutin were identified or tentatively characterized according to the results of retention time and MS spectra, which is highly consistent with our previous reports that quercetin and rutin are potent protective agents against glomerulosclerosis in DN. Therefore, all these results indicate that target cell extraction coupled with LC-MS/MS analysis can be successfully applied for predicting the bioactive components in GBE with preventive effect against DN.

Two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to study the excretion and metabolic interaction of edaravone and taurine in rats.

In this study, two independent and complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the determination of edaravone or taurine in rat urine, feces and bile after intravenous administration, using 3-methyl-l-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Edaravone was separated on an Agilent Eclipse Plus C18 column (100×2.1 mm, 3.5 µm) using methanol and water (containing 5 mM ammonium formate and 0.02% formic acid) as mobile phase, while taurine was performed on a Waters Atlantis HILIC Silica column (150×2.1 mm, 3 µm) using acetonitrile and water (containing 5mM ammonium formate and 0.2% formic acid) as mobile phase. The mass analysis was performed in a Triple Quadrupole mass spectrometer via multiple reaction monitoring (MRM) with negative ionization mode. The optimized mass transition ion pairs (m/z) for quantification were 173.1→92.2 and 187.2→106.0 for edaravone and its IS, 124.1→80.0 and 172.0→80.0 for taurine and its IS, respectively. The validated methods have been successfully applied to the excretion and metabolism interaction study of edaravone and taurine in rats after independent intravenous administration and co-administration with a single dose. The results demonstrated that there were no significant alternations on the metabolism and cumulative excretion rate of edaravone and taurine, implying that the proposed combination therapy was pharmacologically viable.