Combinatorial metabolic engineering of Streptomyces sp. CB03234-S for the enhanced production of anthraquinone-fused enediyne tiancimycins.

BACKGROUND: Anthraquinone-fused enediynes (AFEs) are excellent payloads for antibody-drug conjugates (ADCs). The yields of AFEs in the original bacterial hosts are extremely low. Multiple traditional methods had been adopted to enhance the production of the AFEs. Despite these efforts, the production titers of these compounds are still low, presenting a practical challenge for their development. Tiancimycins (TNMs) are a class of AFEs produced by Streptomyces sp. CB03234. One of their salient features is that they exhibit rapid and complete cell killing ability against various cancer cell lines. RESULTS: In this study, a combinatorial metabolic engineering strategy guided by the CB03234-S genome and transcriptome was employed to improve the titers of TNMs. First, re-sequencing of CB03234-S (Ribosome engineered mutant strains) genome revealed the deletion of a 583-kb DNA fragment, accounting for about 7.5% of its genome. Second, by individual or combined inactivation of seven potential precursor competitive biosynthetic gene clusters (BGCs) in CB03234-S, a double-BGC inactivation mutant, S1009, was identified with an improved TNMs titer of 28.2 ± 0.8 mg/L. Third, overexpression of five essential biosynthetic genes, including two post-modification genes, and three self-resistance auxiliary genes, was also conducted, through which we discovered that mutants carrying the core genes, tnmE or tnmE10, exhibited enhanced TNMs production. The average TNMs yield reached 43.5 ± 2.4 mg/L in a 30-L fermenter, representing an approximately 360% increase over CB03234-S and the highest titer among all AFEs to date. Moreover, the resulting mutant produced TNM-W, a unique TNM derivative with a double bond instead of a common ethylene oxide moiety. Preliminary studies suggested that TNM-W was probably converted from TNM-A by both TnmE and TnmE10. CONCLUSIONS: Based on the genome and transcriptome analyses, we adopted a combined metabolic engineering strategy for precursor enrichment and biosynthetic pathway reorganization to construct a high-yield strain of TNMs based on CB03234-S. Our study establishes a solid basis for the clinical development of AFE-based ADCs.

Programming Intracellular Clustering of Spiky Nanoparticles via Liposome Encapsulation.

The intracellular clustering of anisotropic nanoparticles is crucial to the improvement of the localized surface plasmon resonance (LSPR) for phototherapy applications. Herein, we programmed the intracellular clustering process of spiky nanoparticles (SNPs) by encapsulating them into an anionic liposome via a frame-guided self-assembly approach. The liposome-encapsulated SNPs (lipo-SNPs) exhibited distinct and enhanced lysosome-triggered aggregation behavior while maintaining excellent monodispersity, even in acidic or protein-rich environments. We explored the enhancement of the photothermal therapy performance for SNPs as a proof of concept. The photothermal conversion efficiency of lipo-SNPs clusters significantly increased 15 times compared to that of single lipo-SNPs. Upon accumulation in lysosomes with a 2.4-fold increase in clustering, lipo-SNPs resulted in an increase in cell-killing efficiency to 45% from 12% at 24 µg/mL. These findings indicated that liposome encapsulation provides a promising approach to programing nanoparticle clustering at the target site, which facilitates advances in the development of smart nanomedicine with programmable enhancement in LSPR.

Distribution and Elimination of Deltamethrin Toxicity in Laying Hens.

Deltamethrin, an important pyrethroid insecticide, is frequently detected in human samples. This study aims to assess the potential effects of deltamethrin on human health and investigate the patterns of residue enrichment and elimination in 112 healthy laying hens. These hens were administered 20 mg·kg-1 deltamethrin based on their body weight. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the residue enrichment pattern and elimination pattern of deltamethrin in the hens. The results indicated a significant increase in the concentration of deltamethrin in chicken manure during the treatment period. By the 14th day of administration, the concentration of deltamethrin in the stool reached 13,510.9 ± 172.24 µg·kg-1, with a fecal excretion rate of 67.56%. The pulmonary deltamethrin concentration was the second highest at 3844.98 ± 297.14 µg·kg-1. These findings suggest that chicken feces contain substantial amounts of deltamethrin after 14 days of continuous administration, and that it can easily transfer to the lungs. After 21 days of drug withdrawal, the residual concentration of deltamethrin in the fat of laying hens was 904.25 ± 295.32 µg·kg-1, with a half-life of 17 days and a slow elimination rate. In contrast, the lungs showed relatively low elimination half-lives of 0.2083 days, indicating faster elimination of deltamethrin in this tissue. These results highlight differences in the rate of deltamethrin elimination in different tissues during drug withdrawal. The fat of laying hens exhibited the highest residue of deltamethrin and the slowest elimination rate, while the lungs showed the fastest elimination rate. Moreover, deltamethrin was found to accumulate in the edible tissues of eggs and laying hens, suggesting that humans may be exposed to deltamethrin through food.

Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.

SCOPE: Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta-analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta-analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population. METHODS AND RESULTS: Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full-text assessment and included 1517 subjects. Double-blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: -0.40, 95% CI: [-0.67 to -0.13], p = 0.003), IL-6 (SMD: -0.67, 95% CI: [-1.01 to -0.33], p < 0.001), and TNF-α (SMD: -1.06, 95% CI: [-1.59 to -0.52], p < 0.001) and increase the concentration of circulating CoQ10. CONCLUSION: This meta-analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300-400 mg CoQ10 show superior inhibition of inflammatory factors.

Comparison of the total and hidden blood loss in patients undergoing single-level open and unilateral biportal endoscopic transforaminal lumbar interbody fusion: a retrospective case control study.

PURPOSE: This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF). METHODS: A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler's formula was employed to estimate the patient's blood volume (PBV), Gross's formula to estimate TBL, and Sehat's formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance. RESULTS: TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group. CONCLUSIONS: Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.

Mid-term study on the effects of arthroscopic discoid lateral meniscus plasty on patellofemoral joint: An observational study.

In the present study, we aimed to investigate the clinical outcomes of arthroscopic discoid lateral meniscus (DLM) plasty and the adaptive changes in the patellofemoral joint after surgery. From September 2010 to March 2012, 25 patients with DLM injuries who underwent arthroscopic meniscus plasty were enrolled in the prospective study. All patients underwent clinical evaluation before the operation and at the last follow-up, and imaging evaluation was performed by upright magnetic resonance imaging before and 1 month after the operation as well as at the last follow-up. Clinical evaluation included Lysholm score, Kujala score, McMurray's sign, patellar mobility, patella grind test, and quadriceps atrophy. Imaging evaluation included bisect offset index, patella tilt angle (PTA), and cartilage damage. Lysholm score, Kujala score, McMurray's sign, and quadriceps atrophy at the last follow-up were significantly improved compared with the preoperative levels (P < .05). At the last follow-up, there were no statistical differences in patella mobility and patella grind test compared with the preoperative levels. In addition, bisect offset index and PTA showed a dynamic trend of rising and then falling over time (P < .05). At 1 month after the operation, bisect offset index and PTA were significantly increased compared with the preoperative levels or the values at the last follow-up (P < .05), while there were no differences between the preoperation and the last follow-up. Cartilage damage became worse with time (P < 0.05), and the 2 were positively correlated (Spearman = 0.368). At the last follow-up, the degree of cartilage damage was significantly increased compared with the preoperative level (P < .017), while there was no significant difference between the 1-month postoperative grade and the preoperational grade or the last follow-up grade. The effect of arthroscopic DLM plasty on the patellofemoral joint was dynamic, with the position of the patella deviating in the early stages and recovering in the mid-term, especially when the knee was in the biomechanical standing position. In addition, the patellofemoral joint cartilage might undergo accelerated degeneration after the operation, while the mid-term effect of the operation was positive, and the patellofemoral joint function was acceptable.

J-Shaped Association of Tomato Intake with New-Onset Hypertension in General Adults: A Nationwide Prospective Cohort Study.

We aim to examine the prospective association between the intake of dietary tomatoes and the risk of new-onset hypertension and its modifiable factors in general adults. A total of 11,460 adults without hypertension from the China Health and Nutrition Survey (CHNS) were enrolled, with follow-up beginning in 1997 and ending in 2015. Dietary tomato intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or diagnosed by physicians or under anti-hypertensive treatment during the follow-up. Finally, 4015 subjects developed new-onset hypertension during 92,335.5 person-years of follow-up. After multivariate adjustment for dietary and non-dietary risk factors, hazard ratios for increased consumption of dietary tomatoes were 0.42 (95% confidence interval, 0.37−0.47), 0.51 (0.46−0.57), and 0.82 (0.74−0.92) compared with non-consumers. Overall, cubic spline regression suggested a novel J-shaped association between dietary tomato intake and new-onset hypertension, with the lowest risk observed at approximately 10 to 13 g/day (p < 0.001 for curvature). Moreover, the association between dietary tomato intake and risk of new-onset hypertension was stronger in females or individuals who refrained from smoking or drinking (p = 0.024, p = 0.043, and p = 0.044 for interaction, respectively).

Medium optimization and subsequent fermentative regulation enabled the scaled-up production of anti-tuberculosis drug leads ilamycin-E1/E2.

BACKGROUND: Tuberculosis (TB) and its evolving drug resistance have exerted severe threats on the global health, hence it is still essential to develop novel anti-TB antibiotics. Ilamycin-E1/E2 is a pair of cycloheptapeptide enantiomers obtained from a marine Streptomyces atratus SCSIO ZH16-ΔilaR mutant, and has presented significant anti-TB activities as promising drug lead compounds, but their clinical development has been hampered by low fermentation titers. MAIN METHODS AND MAJOR RESULTS: By applying the statistical Plackett-Burman design (PBD) model, bacterial peptone was first screened out as the only significant but negative factor to affect the ilamycin-E1/E2 production. Subsequent single factor optimization in shaking flasks revealed that the replacement of bacterial peptone with malt extract could not only eliminate the accumulation of porphyrin-type competitive byproducts but also improve the titer of ilamycin-E1/E2 from original 13.6 ± 0.8 to 142.7 ± 5.7 mg L-1 , about 10.5-fold increase. Next, a pH coordinated feeding strategy was adopted in 30 L fermentor and obtained 169.8 ± 2.5 mg L-1 ilamycin-E1/E2, but further scaled-up production in 300 L fermentor only gave a titer of 131.5 ± 7.5 mg L-1 due to the unsynchronization of feeding response and pH change. Consequently, a continuous pulse feeding strategy was utilized in 300 L fermentor to solve the above problem and finally achieved 415.7 ± 29.2 mg L-1 ilamycin-E1/E2, representing a 30.5-fold improvement. IMPLICATION: Our work has provided a solid basis to acquire sufficient ilamycin-E1/E2 lead compounds and then support their potential anti-TB drug development.

LncRNA SNHG16 promotes Schwann cell proliferation and migration to repair sciatic nerve injury.

BACKGROUND: To investigate the expression of long non-coding RNA (lncRNA) Snorna hostgene16 (SNHG16) in sciatic nerve injury tissues and cells. The molecular mechanism of SNHG16 regulating signal activator of transcription 3 (STAT3) expression through "sponge" adsorption of miR-93-5p was also studied. METHODS: A rat model of sciatic nerve injury was established, and primary Schwann cells (SCs) were extracted. The expression of SNHG16 in animal tissues with sciatic nerve injury and SCs treated with ischemia and hypoxia was detected by qPCR, and CCK-8 assay, cell scratch assay, and Transwell chamber assay were used to detect cell proliferation, migration, and invasion. The targeted binding of SNHG16 to miR-93-5p was verified by double luciferase reporter gene assay and miRNA immunoprecipitation assay. MiR-93-5p mimic, SNHG16 overexpression vector, and sh-STAT3 plasmid were transfected into cells, respectively, and the mRNA expressions of SNHG16, miR-93-5p, and STAT3 in the cells were detected by qPCR. RESULTS: The expression of lncRNA SNHG16 was decreased after sciatic nerve injury, while overexpression of SNHG16 promoted the proliferation, migration, and invasion of SCs. The results of dual luciferase reporter gene assay and miRNA immunoprecipitation reaction showed miR-93-5p interacted with SNHG16, and the overexpression of miR-93-5p reversed the promoting effects of SNHG16 on the proliferation and invasion of SCs. At the same time, the knockdown of STAT3, which is the target gene of miR-93-5p, reversed the proliferation and invasion promotion effect of SNHG16 on SCs. SNHG16 affected the expression of its downstream target gene STAT3 by adsorbing miR-93-5p via endogenous competitive sponge. CONCLUSIONS: SNHG16 can regulate STAT3 expression by sponge adsorption of miR-93-5p in SCs, and SNHG16 and miR-93-5p can be used as potential targets for the diagnosis and treatment of sciatic nerve injury.

Dexmedetomidine improves oxygen-glucose deprivation/reoxygenation (OGD/R) -induced neurological injury through regulating SNHG11/miR-324-3p/VEGFA axis.

Dexmedetomidine (Dex) has been reported to exhibit neuroprotective effects through various regulatory mechanisms. This study aims to investigate the role and molecular mechanism of SNHG11 in Dex-mediated neuroprotection. The ischemic stroke (IS) model was established in vivo by middle cerebral artery occlusion (MCAO) and in vitro by oxygen-glucose deprivation and reperfusion (OGD/R)-treated SH-SY5Y. SNHG11 was highly expressed after OGD/R, and Dex improved OGD/R-induced neurological injury. Additionally, Dex reversed the effects of SNHG11 on OGD/R-induced neurological injury. Furthermore, we found that SNHG11 upregulated vascular endothelial growth factor A (VEGFA) expression by targeting miR-324-3p. Through rescue assays, it was confirmed that SNHG11 regulated OGD/R-induced neurological injury through increasing VEGFA expression. At last, Dex was also discovered to improve neurological injury through regulating SNHG11 in the rat model. In conclusion, our work demonstrated that Dex improved OGD/R-induced neurological injury via SNHG11/miR-324-3p/VEGFA axis. These findings may offer a novel therapeutic strategy for IS treatment.

Defect Engineering of Copper Paddlewheel-Based Metal-Organic Frameworks of Type NOTT-100: Implementing Truncated Linkers and Its Effect on Catalytic Properties.

A series of new defect-engineered metal-organic frameworks (DEMOFs) were synthesized by framework doping with truncated linkers employing the mixed-linker approach. Two tritopic defective (truncated) linkers, biphenyl-3,3',5-tricarboxylates (LH) lacking a ligating group and 5-(5-carboxypyridin-3-yl)isophthalates (LPy) bearing a weaker interacting ligator site, were integrated into the framework of Cu2(BPTC) (NOTT-100, BPTC = biphenyl-3,3',5,5'-tetracarboxylates). Incorporating LH into the framework mainly generates missing metal node defects, thereby obtaining dangling COOH groups in the framework. However, introducing LPy forms more modified metal nodes featuring reduced and more accessible Cu sites. In comparison with the pristine NOTT-100, the defect-engineered NOTT-100 (DE-NOTT-100) samples show two unique features: (i) functional groups (the protonated carboxylate groups as the Brønsted acid sites or the pyridyl N atoms as the Lewis basic sites), which can act as second active sites, are incorporated into the MOF frameworks, and (ii) more modified paddlewheels, which provided extra coordinatively unsaturated sites, are generated. The cooperative functioning of the above characteristics enhances the catalytic performance of certain types of reactions. For a proof of concept, two exemplary reactions, namely, the cycloaddition of CO2 with propylene oxide to propylene carbonate and the cyclopropanation of styrene, were carried out to evaluate the catalytic activities of those DE-NOTT-100 materials depending on the defect structure.

Antitubercular Ilamycins from Marine-Derived Streptomyces atratus SCSIO ZH16 ΔilaR.

Tuberculosis (TB) ranks as the leading cause of death from a single infectious agent (ranking more lethal than HIV/AIDS) over the course of the past decade. More concerning is that reports of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB have been dramatically increasing. It continues to become ever more clear that novel anti-TB drugs with improved efficacies and reduced toxicities are urgently needed. We report here the discovery of 12 new ilamycin analogues, ilamycins G-R (1-12), bearing various nonproteinogenic amino acids, along with ilamycins E1 (13) and F (14), from a 200 L scale culture of the marine-derived mutant actinomycete Streptomyces atratus SCSIO ZH16 ΔilaR. Importantly, bioassays against Mycobacterium tuberculosis H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 µM. The structures of 1-12 were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound 10 was found to be moderately cytotoxic against a panel of tumor human cell lines. From these data we can formulate tentative structure-activity relationships for the antitubercular and antitumor activities of the ilamycins.

Defect Creation in Surface-Mounted Metal-Organic Framework Thin Films.

Defect engineering is a strategy for tailoring the properties of metal-organic frameworks (MOFs). Plenty of efforts have been devoted to study the defect chemistry and structures of bulk MOFs; however, the reported example of a defect-engineered surface-mounted MOF (SURMOF) thin film is rare. In this work, defects were incorporated in SURMOF thin films by using defect-generating linkers and taking advantage of the liquid-phase stepwise epitaxial layer-by-layer growth (LBL). Two methods based on the LBL, named mixing method and alternating method, are proposed for incorporating defects in the prototypical SURMOF HKUST-1 by partially substituting the parent H3btc (benzene-1,3,5-tricarboxylic acid) linker with a set of defect-generating linkers H2ip (isophthalic acid), H2OH-ip (5-hydroxyisophthalic acid), and H2pydc (3,5-pyridinedicarboxylic acid). The crystallinity and phase purity of the obtained "defected" SURMOFs were confirmed by X-ray diffraction, infrared reflection absorption spectroscopy, and Raman spectroscopy. The incorporation of the defect-generating linkers and the types of induced defects were characterized by ultraviolet-visible spectroscopy, time-of-flight secondary ion mass spectrometry, methanol adsorption, scanning electron microscopy, and 1H nuclear magnetic resonance spectroscopy (after digestion of the samples). These two methods provide avenues for controlling the defect formation in MOF thin films.

Rapid determination of sulfonamides in chicken using two-dimensional online cleanup mode with three columns coupled to liquid chromatography-tandem mass spectrometry.

A novel method based on online cleanup mode combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established. After an automated sample cleanup system with aqueous gel column, sulfonamides in chicken were detected in multiple reaction monitoring (MRM) mode. The total run time of the system, which included automated extraction, analytical chromatography and re-equilibration, was within 30 min. Different experimental processes containing extraction, purification, separation, and detection have been evaluated respectively to obtain optimized parameters. The developed method was fully validated and the efficient and superior performance of the developed method was demonstrated. The method produced linear results for all sulfonamides from 1 to 10 ng g-1 with a linearity >0.99. The intra-day precision of the method was <8.45% while the inter-day precision was <9.11%. The matrix effect was 77.5% to 105.1%. The recovery was in the range of 72.66% to 116.7% for all sulfonamides. The limit of quantitation in the chicken was 0.6 ng g-1 and the limit of detection was 0.2 ng g-1. Compared with traditional procedures, the automated sample clean-up strategy could significantly shorten the analysis time and offer higher detectability, with the advantage of sufficient sensitivity. Also, the use of gel chromatography column employed the water phase and reduced the organic reagent to achieve the level of green chemistry.

AIEgen-Functionalized Mesoporous Silica Gated by Cyclodextrin-Modified CuS for Cell Imaging and Chemo-Photothermal Cancer Therapy.

A novel multifunctional drug delivery system has been constructed by assembling per-6-thio-ß-cyclodextrin-modified ultrasmall CuS nanoparticles (CD-CuS) onto fluorescent AIEgen-containing mesoporous silica nanoparticles (FMSN). The CD-CuS nanoparticles are anchored on the surface of benzimidazole-grafted FMSN, acting as a gatekeeper and photothermal agent. The prepared blue-emitting nanocomposite (FMSN@CuS) exhibits good biocompatibility and cell imaging capability. Anticancer drug doxorubicin hydrochloride (DOX) molecules are loaded into FMSN@CuS, and zero prerelease at physiological pH (7.4) and on-demand drug release at an acidic environment can be achieved due to the pH-responsive gate-opening of CD-CuS only at an acidic condition. The FMSN@CuS nanocomposite can generate obvious thermal effect after the exposure of 808 nm laser, which can also accelerate the DOX release. Meanwhile, the fluorescence intensity of DOX-loaded FMSN@CuS increases with the release of DOX, and the intracellular drug release process can be tracked according to the change of luminescence intensity. More importantly, DOX-loaded FMSN@CuS displays efficient anticancer effects in vitro upon 808 nm laser irradiation, demonstrating a good synergistic therapeutic effect via combining enhanced chemotherapy and photothermal therapy.

AIE Luminogen-Functionalized Hollow Mesoporous Silica Nanospheres for Drug Delivery and Cell Imaging.

Hollow mesoporous silica nanospheres functionalized with aggregation-induced emission (AIE) luminogen tetraphenylethene were prepared by postgrafting method. The as-prepared inorganic-organic hybrid nanospheres show bright blue emission and good biocompatibility as shown by MTT assays. The large cavities of the materials enable high loading of the anticancer drug doxorubicin hydrochloride (DOX), and the mesoporous silica shells allow pH-dependent drug release. The materials can be effectively taken up by cells and function as luminescent bioprobes, demonstrating their potential application in imaging-guided therapy.

Pharmacokinetics and tissue distribution study of ginkgolide L in rats by ultra-high performance liquid chromatography coupled with tandem mass spectrometry.

An ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) approach was developed and validated for the determination of ginkgolide L (GL) in rat plasma and tissues using diazepam as internal standard (IS). Detection was performed on a triple quadrupole MS system using multiple reaction monitoring (MRM) mode in positive mode. Sample preparation was carried out through a liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved by using an Agilent ZORBAX SB-Aq column with a mobile phase of 0.5% aqueous formic acid (A) and methanol (B). The monitored transitions were set at m/z 391.14→271.10 for GL and m/z 285.08→193.10 for IS, respectively. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of GL in rats after intravenous administration. Good linearity was found between 2.5-2000ng/mL (r>0.996) for plasma samples, and calibration curves were also linear for other tissue samples over a wide range. The results indicated that GL has linear pharmacokinetic properties after intravenous administration at three doses. GL could distribute to tissues quickly and the major distribution tissue of GL in rats was liver. This was the first report of pharmacokinetic and tissue distribution data for GL.

Determination of the Elasticity of Breast Tissue during the Menstrual Cycle Using Real-Time Shear Wave Elastography.

We examined breast tissue elasticity during the menstrual cycle using real-time shear wave elastography (RT-SWE), a recent technique developed for soft tissue imaging. Written informed consent for RT-SWE was obtained from all eligible patients, who were healthy women aged between 19 and 52 y. Young's moduli of the breast tissue in the early follicular, late phase and luteal phase were compared. There were no significant differences in the mean, maximum and minimum elasticity values (Emean, Emax and Emin) and standard deviation (ESD). RT-SWE of glandular tissue revealed that ESD was increased in the early follicular phase compared with the luteal phase. Means ± SD of Emin, Emax and Emean in glandular tissue were 5.174 ± 2.138, 8.308 ± 3.166 and 6.593 ± 2.510, respectively, and in adipose tissue, 3.589 ± 2.083, 6.733 ± 3.522 and 4.857 ± 2.564, respectively. There were no significant differences in stiffness between glandular and adipose tissues throughout the menstrual cycle, but glandular tissue stiffness was lower in the luteal phase than in the early follicular phase. On the basis of these observations in normal healthy women, we believe we have obtained sufficient information to establish the baseline changes in human breast elasticity during the menstrual cycle. In the future, we intend to compare the elasticity values of healthy breast tissue with those of breast tissue affected by various pathologies. Our results reveal the significant potential of RT-SWE in the rapid and non-invasive clinical diagnosis of breast diseases, such as breast cancers.

AIE luminogen-functionalised mesoporous nanomaterials for efficient detection of volatile gases.

Mesoporous silica nanoparticles functionalised with aggregation-induced emission (AIE) luminogen via a carbon-nitrogen double bond are fabricated into films by a dip-coating method. The as-made films can serve as efficient fluorescent sensors for the naked-eye detection of volatile acid gases by colour and emission changes, as well as for the detection of 2,4-dinitrotoluene vapours by fluorescence quenching.

Accurate analysis of ginkgolides and their hydrolyzed metabolites by analytical supercritical fluid chromatography hybrid tandem mass spectrometry.

Hydrolysis plays an important role in the metabolic transformations of lactones. Analysis of lactones and their hydrolyzed metabolites in biological samples is challenging, because unexpected hydrolysis or reversed dehydration may occur depending on the test environments. In this work, a supercritical fluid chromatography hybrid triple-quadrupole mass spectrometry (SFC-QQQ MS) method has been proposed for simultaneous analysis of ginkgolides and hydrolyzed metabolites. The SFC utilizes carbon dioxide as the mobile phase, avoiding hydrolysis of ginkgolides that always happens during reversed phase liquid chromatographic detection. Compared with normal phase liquid chromatography, the SFC provides good resolutions especially for ginkgolide with similar structures. This SFC-QQQ MS method was validated in linearity, precision, accuracy, and stability for ginkgolides and metabolites. Then this method was successfully applied to pharmacokinetic study of 3 ginkgolides and their 6 hydrolyzed metabolites after intravenous administration of total ginkgolide extract. Ginkgolides and metabolites showed different clear rates and excluded in 2-4h. The developed SFC-QQQ MS method allows accurate determination of ginkgolides and metabolites with high resolutions, and can be extended to analysis of other water-unstable compounds.