Bioinspired zero-energy thermal-management device based on visible and infrared thermochromism for all-season energy saving.

Radiative thermal management provides a zero-energy strategy to reduce the demands of fossil energy for active thermal management. However, whether solar heating or radiative cooling, one-way temperature control will exacerbate all-season energy consumption during hot summers or cold winters. Inspired by the Himalayan rabbit's hair and Mimosa pudica's leaves, we proposed a dual-mode thermal-management device with two differently selective electromagnetic spectrums. The combination of visible and infrared "thermochromism" enables this device to freely switch between solar heating and radiative cooling modes by spontaneously perceiving the temperature without any external energy consumption. Numerical prediction shows that a dual-mode device exhibits an outstanding potential for all-season energy saving in terms of thermal management beyond most static or single-wavelength, range-regulable, temperature-responsive designs. Such a scalable and cost-efficient device represents a more efficient radiative thermal-management strategy toward applying in a practical scenario with dynamic daily and seasonal variations.

O-GlcNAc participates in the meiosis of aging oocytes by mediating mitochondrial function.

With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases, yet it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (32-34 weeks) which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 (DRP1) to meditate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and OGA knockdown (OGA-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 week-old mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging.

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy.

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

Highly Antifreezing Thermogalvanic Hydrogels for Human Heat Harvesting in Ultralow Temperature Environments.

Thermogalvanic hydrogels have been quickly developed and are widely used in thermal energy harvesting. However, the freezing behaviors of thermogalvanic hydrogels at subzero temperatures greatly limit their practical applications. Herein, we design an antifreezing thermogalvanic hydrogel based on [Fe(CN)6]3-/4- ions for thermoelectric power generation in ultralow temperature environments. The antifreezing thermogalvanic hydrogels show excellent flexibility at -80 °C owing to the hydrogen bonding between ethylene glycol and water molecules. Even after 500 cyclic tensile strains, the thermogalvanic hydrogels can still maintain excellent mechanical stability, and the Seebeck coefficient is as high as 1.43 mV/K, corresponding to a large retention rate of ∼95%. Moreover, we demonstrate a wearable thermoelectric shoe based on antifreezing thermogalvanic hydrogels for harvesting human thermal energy in a simulated winter environment of -30 °C, and the electricity can drive a green LED. This work provides important guidance for the design and optimization of antifreezing thermogalvanic hydrogels.

Maternal RNA binding protein with multiple splicing 2 (RBPMS2) is involved in mouse blastocyst formation through the bone morphogenetic protein pathway.

RESEARCH QUESTION: Is early embryo development in mice influenced by RNA binding protein with multiple splicing 2 (RBPMS2), a maternal factor that accumulates and is stored in the cytoplasm of mature oocytes? DESIGN: The expression patterns of RBPMS2 in mouse were analysed using quantitative real-time PCR (qRT PCR) and immunofluorescence staining. The effect of knockdown of RBPMS2 on embryo development was evaluated through a microinjection of specific morpholino or small interfering RNA. RNA sequencing was performed for mechanistic analysis. The interaction between RBPMS2 and the bone morphogenetic protein (BMP) pathway was studied using BMP inhibitor and activator. The effect on the localization of E-cadherin was determined by immunofluorescence staining. RESULTS: Maternal protein RBPMS2 is highly expressed in mouse oocytes, and knockdown of RBPMS2 inhibits embryo development from the morula to the blastocyst stage. Mechanistically, RNA sequencing showed that the differentially expressed genes were enriched in the transforming growth factor-ß (TGF-ß) signalling pathway. BMPs are members of the TGF-ß superfamily of growth factors. It was found that the addition of BMP inhibitor to the culture medium led to a morula-stage arrest, similar to that seen in RBPMS2 knockdown embryos. This morula-stage arrest defect caused by RBPMS2 knockdown was partially rescued by BMP activator. Furthermore, the localization of E-cadherin to the membrane was impaired in response to a knockdown of RBPMS2 or inhibition of the BMP pathway. CONCLUSION: This study suggests that RBPMS2 activates the BMP pathway and thus influences the localization of E-cadherin, which is important for early mouse embryo development during blastocyst formation.

LncRNA Tug1 maintains blood-testis barrier integrity by modulating Ccl2 expression in high-fat diet mice.

Sertoli cells are essential for spermatogenesis in the testicular seminiferous tubules by forming blood-testis barrier (BTB) and creating a unique microenvironment for spermatogenesis. Many lncRNAs have been reported to participate in spermatogenesis. However, the role of long noncoding RNAs (lncRNAs) in Sertoli cells has rarely been examined. Herein, we found that a high-fat diet (HFD) decreased sperm quality, impaired BTB integrity and resulted in accumulation of saturated fatty acids (SFAs), especially palmitic acid (PA), in mouse testes. PA decreased the expression of tight junction (TJ)-related proteins, increased permeability and decreased transepithelial electrical resistance (TER) in primary Sertoli cells and TM4 cells. Moreover, lncRNA Tug1 was found to be involved in PA-induced BTB disruption by RNA-seq. Tug1 depletion distinctly impaired the TJs of Sertoli cells and overexpression of Tug1 alleviated the disruption of BTB integrity induced by PA. Moreover, Ccl2 was found to be a downstream target of Tug1, and decreased TJ-related protein levels and TER and increased FITC-dextran permeability in vitro. Furthermore, the addition of Ccl2 damaged BTB integrity after overexpression of Tug1 in the presence of PA. Mechanistically, we found that Tug1 could directly bind to EZH2 and regulate H3K27me3 occupancy in the Ccl2 promoter region by RNA immunoprecipitation and chromatin immunoprecipitation assays. Our study revealed an important role of Tug1 in the BTB integrity of Sertoli cells and provided a new view of the role of lncRNAs in male infertility.

Photonic-Structure Colored Radiative Coolers for Daytime Subambient Cooling.

Daytime subambient radiative cooling provides a powerful strategy for realizing sustainable thermal management without any external energy consumption. However, in practical situations a dazzling white or silver appearance is undesirable for aesthetic and functional reasons. Therefore, developing colored radiative cooling materials is greatly significant for more potential applications but remains a big challenge so far. Here, we reported a flexible colored radiative cooler based on interferometric retroreflection-induced structural color, which resolves the conflict between a colorful appearance for aesthetics and high solar reflection for cooling. All colored radiative coolers achieve subambient cooling of 4 K even under sunshine stronger than 1000 W/m2, while the same color commercial paints are 9-27 K higher than the ambient. Such a flexible, scalable, and low cost colored radiative cooler is expected to replace commercial paint in a practical scenario with aesthetic and cooling requirements, enabling substantial reduction in carbon emission and energy consumption.

Multifunctional Superelastic Graphene-Based Thermoelectric Sponges for Wearable and Thermal Management Devices.

Power generation through harvesting human thermal energy provides an ideal strategy for self-powered wearable design. However, existing thermoelectric fibers, films, and blocks have small power generation capacity and poor flexibility, which hinders the development of self-powered wearable electronics. Here, we report a multifunctional superelastic graphene-based thermoelectric (TE) sponge for wearable electronics and thermal management. The sponge has a high Seebeck coefficient of 49.2 µV/K and a large compressive strain of 98%. After 10 000 cyclic compressions at 30% strain, the sponge shows excellent mechanical and TE stability. A wearable sponge array TE device was designed to drive medical equipment for monitoring physiological signals by harvesting human thermal energy. Furthermore, a 4 × 4 array TE device placed on the surface of a normal working Central Processing Unit (CPU) can generate a stable voltage and reduce the CPU temperature by 8 K, providing a feasible strategy for simultaneous power generation and thermal management.

Giant Room-Temperature Electrocaloric Effect of Polymer-Ceramic Composites with Orientated BaSrTiO3 Nanofibers.

Cooling based on the electrocaloric effect (ECE) is a promising solution to environmental and energy efficiency problems of vapor-compression refrigeration. Ferroelectric polymer-ceramics nanocomposites, integrating high electric breakdown of organic ferroelectrics and large EC strength of ceramics, are attractive EC materials. Here, we tuned the orientation of Ba0.67Sr0.33TiO3 nanofibers (BST nfs) in the P(VDF-TrFE-CFE) polymer. When the nfs were aligned parallel to the field, a ΔT of 11.3 K with an EC strength of 0.16 K·m/MV was achieved in the blends. The EC strength not only surpasses advanced nanocomposites but also is comparable to ferroelectric ceramics. The simulation indicates that a significantly higher electric field is concentrated in polymer regions around the ends of the orientated nfs, contributing to easier flipping of polymer chains for large ECE. This work provides a new method to obtain large ECE in composites for next-generation refrigeration.

High-Performance Coaxial Asymmetry Fibrous Supercapacitors with a Poly(vinyl alcohol)-Montmorillonite Separator.

Fibrous supercapacitors have garnered great interest from researchers because of their large electrode/electrolyte interface area, short ion transport path, and high flexibility. However, obtaining a thin gel electrolyte interlayer with a high ion transport rate and uniform thickness is still challenging. Here, we proposed an efficient wet-spinning technique to fabricate uniform polyvinyl-montmorillonite tubular layers for the preparation of a high-performance coaxial asymmetry fibrous supercapacitor (AFSC). The coaxial AFSC shows ultrahigh energy densities in the range of 2.86-4.04 µW h cm-2 at power densities of 0.16-1.61 mW cm-2 while maintaining a long cycling life (94% retention even after 20 000 cycles). After charging at a constant voltage of 2.4 V for 30 s, the flexible watchband which is composed of three series-connected AFSCs could power a commercial electronic watch for more than 2 min. This work provides a universal strategy to fabricate high-performance and wearable energy storage devices.

Highly Stretchable Carbon Nanotubes/Polymer Thermoelectric Fibers.

Thermoelectric (TE) technology provides a new way to directly harvest and convert the heat continuously released from the human body. The greatest challenge for TE materials applied in wearable TE generators is compatible with the constantly changing morphology of the human body while offering a continuous and stable power output. Here, a stretchable carboxylic single-walled carbon nanotube (SWNT)-based TE fiber is prepared by an improved wet-spinning method. The stable Seebeck coefficient of the annealed carboxylic SWNT-based TE fiber is 44 µV/K even under the tensile strain of ∼30%. Experimental results show that the fiber can continue to generate constant TE potential when it is changed to various shapes. The new stretchable TE fiber has a larger Seebeck coefficient and more stretchability than existing TE fibers based on the Seebeck effect, opening a path to using the technology for a variety of practical applications.

[Non-invasive chromosome screening for male infertility patients with severe oligo-astheno-teratozoospermia].

Objective: To explore the value of non-invasive embryo chromosome screening (NICS) in improving the outcomes of clinical pregnancy after assisted reproduction in men with severe oligo-astheno-teratozoospermia (OAT). METHODS: We randomly selected 170 cases of assisted reproduction due to severe OAT from January 2017 to December 2020, 85 undergoing NICS treatmentand the other 85 receiving intracytoplasmic sperm injection (ICSI). We made comparisons between the two groups in the female age, body mass index (BMI), anti-Müllerian hormone level (AMH), basal antral follicle count (AFC), infertility duration, male age, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), sperm DNA fragmentation index (DFI), numbers of oocytes retrieved and high-quality blastocysts, and rates of normal fertilization, clinical pregnancy and abortion. RESULTS: No statistically significant differences were observed between the two groups in the female age, female BMI, AMH, AFC, infertility duration, male age, sperm concentration, percentages of PMS and MNS, sperm DFI, numbers of oocytes retrieved and high-quality blastocysts, or normal fertilization rate (P > 0.05). The rate of definite diagnosis was 88.24%, and that of embryo chromosome euploidy was 48.56% in the NICS group. The rate of clinical pregnancy after selected euploid embryo transfer was significantly higher in the NICS than in the ICSI group (66.28% vs 51.09%, P < 0.05), while that of abortion remarkably lower in the former than in the latter (12.28% vs 29.79%, P < 0.05). CONCLUSIONS: For male infertility patients with severe OAT, NICS technology can improve the rate of clinical pregnancy and reduce the risk of abortion.

NLRP3 promotes endometrial receptivity by inducing epithelial-mesenchymal transition of the endometrial epithelium.

Endometrial receptivity is crucial for successful embryo implantation. It is regulated by multiple factors which include ovarian steroid hormones and the immune microenvironment among others. Nod-Like Receptor Pyrins-3 (NLRP3) is a key intracellular pattern-recognition receptor and a critical component of the inflammasome, which plays an essential role in the development of inflammation and of immune responses. However, the physiological functions of NLRP3 in the endometrium remain largely unclear. This study investigated the physiological and pathological significance of NLRP3 in human endometrial epithelial cell during the implantation window. NLRP3 is highly expressed during the mid-proliferative and mid-secretory phases of the human endometrium and transcriptionally up-regulated by estradiol (E2) through estrogen receptor ß (ERß). In addition, NLRP3 promotes embryo implantation and enhances epithelial-mesenchymal transition (EMT) of Ishikawa (IK) cells via both inflammasome-dependent and inflammasome-independent pathways, which might provide a novel insight into endometrial receptivity and embryo implantation. Our findings suggest that NLRP3, which is transcriptionally regulated by E2, induces epithelial-mesenchymal transition of endometrial epithelial cells and promotes embryo adhesion.

Printable and Stretchable Temperature-Strain Dual-Sensing Nanocomposite with High Sensitivity and Perfect Stimulus Discriminability.

Skin-mountable physical sensors that can individually detect mechanical deformations with high strain sensitivity within a broad working strain range and temperature variations with accurate temperature resolution are a sought-after technology. Herein, a stretchable temperature and strain dual-parameter sensor that can precisely detect and distinguish strain from temperature stimuli without crosstalk is developed, based on a printable titanium carbide (MXene)-silver nanowire (AgNW)-PEDOT:PSS-tellurium nanowire (TeNW) nanocomposite. With this dual-parameter sensor, strain and temperature are effectively transduced into electrically isolated signals through the electrically conductive MXene-AgNW and thermoelectric PEDOT:PSS-TeNW components, respectively. In addition, the synergistic effect between the MXene nanosheets and PEDOT:PSS also greatly enhances the stretchability and sensitivity of the sensing devices. These properties enable the nanocomposite to decouple responses between temperature and strain stimuli with an accurate temperature resolution of 0.2 °C and a gauge factor of up to 1933.3 in a working strain range broader than 60%.

Morphological/nanostructural control toward intrinsically stretchable organic electronics.

The development of intrinsically stretchable electronics poses great challenges in synthesizing elastomeric conductors, semiconductors and dielectric materials. While a wide range of approaches, from special macrostructural engineering to molecular synthesis, have been employed to afford stretchable devices, this review surveys recent advancements in employing various morphological and nanostructural control methods to impart mechanical flexibility and/or to enhance electrical properties. The focus will be on (1) embedding percolation networks of one-dimensional conductive materials such as metallic nanowires and carbon nanotubes in an elastomer matrix to accommodate large external deformation without imposing a large strain along the one-dimensional materials, (2) design strategies to achieve intrinsically stretchable semiconductor materials that include direct blending of semiconductors with elastomers and synthesizing semiconductor polymers with appropriate side chains, backbones, cross-linking networks, and flexible blocks, and (3) employing interpenetrating polymer networks, bottlebrush structures and introducing inclusions in stretchable polymeric dielectric materials to improve electrical performance. Moreover, intrinsically stretchable electronic devices based on these materials, such as stretchable sensors, heaters, artificial muscles, optoelectronic devices, transistors and soft humanoid robots, will also be described. Limitations of these approaches and measures to overcome them will also be discussed.

Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells.

The Sertoli cell is the only somatic cell within the seminiferous tubules, and is vital for testis development and spermatogenesis. Rosiglitazone (RSG) is a member of the thiazolidinedione family and is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. It has been reported that RSG protects various types of cells from fatty acid-induced damage. However, whether RSG serves a protective role in Sertoli cells against palmitic acid (PA)-induced toxicity remains to be elucidated. Therefore, the aim of the present study was to investigate the effect of RSG on PA-induced cytotoxicity in Sertoli cells. MTT assay and Oil Red O staining revealed that RSG ameliorated the PA-induced decrease in TM4 cell viability, which was accompanied by an alleviation of PA-induced lipid accumulation in cells. In primary mouse Sertoli cells, RSG also showed similar protective effects against PA-induced lipotoxicity. Knockdown of PPARγ verified that RSG exerted its protective role in TM4 cells through a PPARγ-dependent pathway. To evaluate the mechanism underlying the protective role of RSG on PA-induced lipotoxicity, the present study analyzed the effects of RSG on PA uptake, and the expression of genes associated with both fatty acid oxidation and triglyceride synthesis. The results demonstrated that although RSG did not affect the endocytosis of PA, it significantly elevated the expression of carnitine palmitoyltransferase (CPT)-1A, a key enzyme involved in fatty acid oxidation, which indicated that the protective effect of RSG may have an important role in fatty acid oxidation. On the other hand, the expression of CPT1B was not affected by RSG. Moreover, the expression levels of diacylglycerol O-acyltransferase (DGAT)-1 and DGAT2, both of which encode enzymes catalyzing the synthesis of triglycerides, were not suppressed by RSG. The results indicated that RSG reduced PA-induced lipid accumulation by promoting fatty acid oxidation mediated by CPT1A. The effect of RSG in protecting cells from lipotoxicity was also found to be specific to Sertoli cells and hepatocytes, and not to other cell types that do not store excess lipid in large quantities, such as human umbilical vein endothelial cells. These findings provide insights into the cytoprotective effects of RSG on Sertoli cells and suggest that PPARγ activation may be a useful therapeutic method for the treatment of Sertoli cell dysfunction caused by dyslipidemia.

Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway.

Intersectins (ITSNs), an evolutionarily conserved adaptor protein family, have been implicated in multiple biologic processes; however, their functions in mammalian oocytes have not been addressed. Here, we report delayed meiotic resumption and defective cytokinesis upon specific depletion of ITSN2 in mouse oocytes. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are readily observed in ITSN2-depleted oocytes. Similarly, a small molecule that targets the Cdc42-ITSN interaction also disrupts oocyte maturation and actin polymerization. Moreover, we find that ITSN2 depletion reduces the activity of Cdc42 in oocytes and, of note, that forced expression of the dominant-positive mutant of Cdc42, in part, prevents the effects of ITSN2 knockdown on actin cap formation. In addition, the localization of WASP and Arp2, the downstream effector proteins of Cdc42, is altered in ITSN2-depleted oocytes accordingly. In summary, our data support a model in which ITSN2 depletion induces the inactivation of Cdc42, which, in turn, influences the distribution and function of Arp2/3 and WASP, consequently disrupting oocyte polarity establishment and meiotic division.-Zhang, J., Ma, R., Li, L., Wang, L., Hou, X., Han, L., Ge, J., Li, M., Wang, Q. Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway.

Nrf2 inhibition affects cell cycle progression during early mouse embryo development.

Brusatol, a quassinoid isolated from the fruit of Bruceajavanica, has recently been shown to inhibit nuclear factor erythroid 2-related factor 2 (Nrf2) via Keap1-dependent ubiquitination and proteasomal degradation or protein synthesis. Nrf2 is a transcription factor that regulates the cellular defense response. Most studies have focused on the effects of Nrf2 in tumor development. Here, the critical roles of Nrf2 in mouse early embryonic development were investigated. We found that brusatol treatment at the zygotic stage prevented the early embryo development. Most embryos stayed at the two-cell stage after 5 days of culture (P < 0.05). This effect was associated with the cell cycle arrest, as the mRNA level of CDK1 and cyclin B decreased at the two-cell stage after brusatol treatment. The embryo development potency was partially rescued by the injection of Nrf2 CRISPR activation plasmid. Thus, brusatol inhibited early embryo development by affecting Nrf2-related cell cycle transition from G2 to M phase that is dependent on cyclin B-CDK1 complex.

Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation.

Pyruvate dehydrogenase kinases (PDKs) modulate energy homeostasis in multiple tissues and cell types, under various nutrient conditions, through phosphorylation of the α subunit (PDHE1α, also known as PDHA1) of the pyruvate dehydrogenase (PDH) complex. However, the roles of PDKs in meiotic maturation are currently unknown. Here, by undertaking knockdown and overexpression analysis of PDK paralogs (PDK1-PDK4) in mouse oocytes, we established the site-specificity of PDKs towards the phosphorylation of three serine residues (Ser232, Ser293 and Ser300) on PDHE1α. We found that PDK3-mediated phosphorylation of Ser293-PDHE1α results in disruption of meiotic spindle morphology and chromosome alignment and decreased total ATP levels, probably through inhibition of PDH activity. Unexpectedly, we discovered that PDK1 and PDK2 promote meiotic maturation, as their knockdown disturbs the assembly of the meiotic apparatus, without significantly altering ATP content. Moreover, phosphorylation of Ser232-PDHE1α was demonstrated to mediate PDK1 and PDK2 action in meiotic maturation, possibly through a mechanism that is distinct from PDH inactivation. These findings reveal that there are divergent roles of PDKs during oocyte maturation and indicate a new mechanism controlling meiotic structure.

Simultaneous determination of ginsenoside Rg1 , Re and notoginsenoside R1 in human plasma by LC-MS/MS and its application in a pharmacokinetic study in Chinese volunteers.

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of ginsenosides Rg1 , Re and notoginsenoside R1 in human plasma. Chromatography was performed on Capcell Pak C18 MG II column using a binary gradient using mobile phase A (5 mm ammonium formate solution) and B (methanol, containing 5 mm ammonium formate) at a flow rate of 0.3 mL/min. The entire chromatographic run time was 3.2 min. Quantification was achieved using multiple reaction monitoring in positive mode using API 3000. This method was validated in terms of specificity, linearity, precision, accuracy, matrix effect and stability. The calibration curves were linear in the concentration range of 0.020-5.00 ng/mL for ginsenosides Rg1 , Re and notoginsenoside R1 . The lower limit of quantification (LLOQ) of this method was 0.020 ng/mL. The intra-run and inter-run precision values were within 12.31% for ginsenoside Rg1 , 14.13% for ginsenoside Re and 11.46% for notoginsenoside R1 at their LLOQ levels. The samples were stable under all tested conditions. This method was successfully applied to study the pharmacokinetics of ginsenoside Rg1 and notoginsenoside R1 in 24 healthy volunteers following oral administration of 200 mg Sanqi Tongshu Enteric-Pellets Capsule.