[An ensemble model for assisting early Alzheimer's disease diagnosis based on structural magnetic resonance imaging with dual-time-point fusion].

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder. Due to the subtlety of symptoms in the early stages of AD, rapid and accurate clinical diagnosis is challenging, leading to a high rate of misdiagnosis. Current research on early diagnosis of AD has not sufficiently focused on tracking the progression of the disease over an extended period in subjects. To address this issue, this paper proposes an ensemble model for assisting early diagnosis of AD that combines structural magnetic resonance imaging (sMRI) data from two time points with clinical information. The model employs a three-dimensional convolutional neural network (3DCNN) and twin neural network modules to extract features from the sMRI data of subjects at two time points, while a multi-layer perceptron (MLP) is used to model the clinical information of the subjects. The objective is to extract AD-related features from the multi-modal data of the subjects as much as possible, thereby enhancing the diagnostic performance of the ensemble model. Experimental results show that based on this model, the classification accuracy rate is 89% for differentiating AD patients from normal controls (NC), 88% for differentiating mild cognitive impairment converting to AD (MCIc) from NC, and 69% for distinguishing non-converting mild cognitive impairment (MCInc) from MCIc, confirming the effectiveness and efficiency of the proposed method for early diagnosis of AD, as well as its potential to play a supportive role in the clinical diagnosis of early Alzheimer's disease.

Real-world treatment patterns and outcomes for patients with advanced hepatocellular carcinoma initially treated with PD-1 inhibitors.

BACKGROUND: Programmed cell death protein-1 (PD-1) inhibitors have shown promising clinical efficacy in treating advanced hepatocellular carcinoma (HCC). However, little evidence exists regarding their treatment patterns and outcomes in real-world practice in China. This study aimed to investigate real-world treatment patterns and outcomes of PD-1 inhibitors as first-line therapies for patients with advanced HCC in China. METHODS: The study population included adult patients with advanced HCC who were initially treated with PD-1 inhibitors from April 2020 to November 2022 in China. Descriptive statistics were used to report first-line treatment patterns and associations between patient characteristics and the most frequently used treatment patterns. The effectiveness of first-line treatment with PD-1 inhibitors was also evaluated according to survival and tumor response. RESULTS: The analyses enrolled 480 patients. The four most frequently used first-line treatment patterns of camrelizumab, tislelizumab, camrelizumab + TACE, and tislelizumab + TACE showed statistical differences in patient characteristics of gender, HBV infection, liver cirrhosis, BCLC stage, and portal vein tumor thrombus (all P < 0.05). However, there was no significant difference in median progression-free survival among the first-line treatments of tislelizumab, camrelizumab, and tislelizumab + TACE (not reached vs. 4.4 months vs. 3.6 months, P = 0.5178). The three groups had similar objective response rates (25.0 % vs. 28.6 % vs. 28.6 %, P = 0.927), and disease control rates (73.1 % vs. 78.6 % vs. 64.3 %, P = 0.573) with no statistical significance. CONCLUSIONS: Our findings provided insights into potential therapeutic strategies of PD-1 inhibitors in first-line settings for advanced HCC in real-world practice in China. It was recommended to consider patient characteristics associated with therapeutic options when making clinical decisions. Prospective randomized controlled studies with larger sample sizes and longer follow-up times were warranted further to verify the potential clinical benefits of PD-1 inhibitors.

Engineering performance of tungsten network reinforced copper matrix composites synthesized by selective laser melting and infiltration.

To solve poor engineering performance of copper-tungsten alloys operated at high temperatures, 3D network tungsten frameworks were prepared using a selective laser melting (SLM) process, and then copper was melted and diffused into these tungsten network structures to form copper matrix composites with different copper contents (i.e. Cu-10vol%W and Cu-30vol%W). Their mechanical/electrical properties and arc ablation performance were characterized. Results showed the obtained CuW composites were dense with good interfacial bonding, and the connected Cu phases formed a heat conduction channel and improved electrical and thermal conductivities of the composites. Electrical conductivities of Cu-30W and Cu-10W composites were 44.7% and 80.3% IACS, and their thermal conductivities at 25°C were 247.5 and 375.4 W/(m·K), respectively. The W-skeleton grid structure in the composites showed enhanced effects on impact toughness and anti-friction/wear resistance. Tensile strengths of Cu-30W and Cu-10W composites measured at 300°C were 95 MPa and 135 MPa, and their impact toughness values were 11.25 and 15.25 J/cm2, respectively. For the arc ablation performance, the copper phase of CuW composite was identified as the key influencing phase, whereas the W skeleton effectively hindered the spread of arc spots, inhibited quick melting of copper phases, and played effective support and protection functions.

W network reinforced Cu matrix composites were prepared by combining 3D printing technology and fusion technology, which significantly improved the thermal and mechanical properties of Cu matrix composites. We find that the interconnected Cu phases improves the thermal properties of the composites, and the mesh W skeleton improves the mechanical properties.

Comparison of the incidence of wound complications with preoperative and postoperative radiotherapy in patients with extremity soft tissue sarcoma resection: A meta-analysis.

We performed a meta-analysis to compare the effect of preoperative and postoperative radiotherapy on wound complications after resection of extremity soft tissue sarcoma (ESTS). A comprehensive computerised search of the PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases was conducted from their inception to August 2023 to identify studies comparing the effect of preoperative and postoperative radiotherapy on wound complications after ESTS resection. Two investigators independently screened the literature, extracted the data, and assessed the quality of the articles. The meta-analysis was performed using RevMan 5.4 software. Nine studies with 1271 patients were included, with 631 and 640 patients in the preoperative and postoperative radiotherapy groups, respectively. The results showed that the incidence of postoperative wound complications after ESTS resection was significantly higher with preoperative radiotherapy than with postoperative radiotherapy (27.26% vs. 12.03%, odds ratio [OR]: 2.88, 95% confidence interval [CI]: 2.12-3.91, p < 0.001). However, the rate of local recurrence of ESTS was significantly lower with preoperative radiotherapy than with postoperative radiotherapy (8.75% vs. 14.81%, OR: 0.57, 95% CI: 0.36-0.91, p = 0.02), and the 3-year overall survival was significantly higher in the preoperative radiotherapy group than in the postoperative radiotherapy group (82.24% vs. 70.04%, OR: 1.97, 95% CI: 1.05-3.71, p = 0.03). This pooled analysis suggests that although preoperative radiotherapy increases the rate of wound complications in ESTS compared with postoperative radiotherapy, it significantly reduces the rate of local recurrence after ESTS resection and improves the overall survival of patients. Owing to the limitations in the number and quality of the included studies, additional prospective cohort studies or randomised controlled trials are required to confirm these findings.

Loss-free tensile ductility of dual-structure titanium composites via an interdiffusion and self-organization strategy.

The deformation-coordination ability between ductile metal and brittle dispersive ceramic particles is poor, which means that an improvement in strength will inevitably sacrifice ductility in dispersion-strengthened metallic materials. Here, we present an inspired strategy for developing dual-structure-based titanium matrix composites (TMCs) that achieve 12.0% elongation comparable to the matrix Ti6Al4V alloys and enhanced strength compared to homostructure composites. The proposed dual-structure comprises a primary structure, namely, a TiB whisker-rich region engendered fine grain Ti6Al4V matrix with a three-dimensional micropellet architecture (3D-MPA), and an overall structure consisting of evenly distributed 3D-MPA "reinforcements" and a TiBw-lean titanium matrix. The dual structure presents a spatially heterogeneous grain distribution with 5.8 µm fine grains and 42.3 µm coarse grains, which exhibits excellent hetero-deformation-induced (HDI) hardening and achieves a 5.8% ductility. Interestingly, the 3D-MPA "reinforcements" show 11.1% isotropic deformability and 66% dislocation storage, which endows the TMCs with good strength and loss-free ductility. Our enlightening method uses an interdiffusion and self-organization strategy based on powder metallurgy to enable metal matrix composites with the heterostructure of the matrix and the configuration of reinforcement to address the strength-ductility trade-off dilemma.

Real-world safety of ulinastatin: a post-marketing surveillance of 11,252 patients in China.

BACKGROUND: The safety assessment of ulinastatin can guide clinical practice. The present study aimed to investigate the real-world safety of ulinastatin in China. METHODS: This multicenter study retrospectively analyzed the post-marketing surveillance data of consecutive patients treated with ulinastatin between August 2014 and June 2017 in the general wards and the intensive care units (ICU) of nine hospitals in China. Adverse drug reactions/adverse drug events (ADRs/ADEs) were collected and evaluated in a post-marketing database. RESULTS: A total of 11,252 consecutive patients were included in the study: 7009 ICU patients and 4243 general ward patients. Eleven patients with ADRs/ADEs were observed, including nine ICU patients and two general ward patients. The clinical manifestations were liver dysfunction (n = 5 ICU cases, n = 1 general case), thrombocytopenia (n = 2 ICU cases, n = 1 general case), leukopenia (n = 1 ICU case), and rash (n = 1 ICU case). During the study period, the drug ADR/ADE rate of ulinastatin injection was 0.98‰ (11/11,252 × 1000‰). Among the 11,252 valid patients, only 327 received ulinastatin in accordance with the drug specifications. After excluding unreasonable drug use, the calculated ADR rate was 3.06‰ (1/327 × 1000‰) (95% confidence interval: 0.0‰-17.1‰). In ICU and general ward patients, the use of other drugs combined with ulinastatin was associated with the occurrence of ADRs/ADEs (100% with ADRs/ADEs vs. 0% in controls, P < 0.001). CONCLUSIONS: The incidence of ADRs/ADEs of ulinastatin is < 5‰. The ADRs/ADEs involved limited organs, mainly the skin, gastrointestinal tract, and blood. In most cases, the ADRs/ADEs gradually alleviated or recovered after drug withdrawal. The inappropriate/off-label use of ulinastatin should be the focus of surveillance.

EGF/EGFR Promotes Salivary Adenoid Cystic Carcinoma Cell Malignant Neural Invasion via Activation of PI3K/AKT and MEK/ERK Signaling.

BACKGROUND: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant cancers of the salivary gland, and 32.4-72.0% of SACC cases exhibit neural invasion (NI); however, the molecular mechanism underlying the high invasion potential of SACC remains unclear. METHODS: The present study investigated the role of epidermal growth factor receptor (EGFR) in the AKT inhibition- or mitogen-activated protein kinase kinase (MEK)-induced NI and epithelialmesenchymal transition (EMT) in SACC cells using EGFR, PI3K, and MEK inhibitors. SACC-83 cell viability was assessed using an MTT assay, and a wound healing assay was performed to evaluate cell migration. Immunohistochemical staining with streptavidin peroxidase was used to detect the positive expression rate of EMT, AKT, phosphorylated (p)-AKT, ERK, and p-ERK proteins. The impact of EGFR, PI3K, and MEK inhibitors on tumor growth and NI was examined in a xenograft model in nude mice. RESULTS: EGF and EGFR are effective in increasing cell viability, migration, and invasion. SACC metastasis is affected by the PI3K/AKT and MEK/ERK pathways, both of which are initiated by EGF/EGFR. The EMT and NI are regulated by the EGF/EGFR, PI3K/AKT, and MEK/ERK pathways. The present findings demonstrate the importance of suppressed EGFR/AKT/MEK signaling in NI in SACC by neural-tumor co-culture in vitro. Furthermore, our preclinical experiment provides solid evidence that injection of EGFR, PI3K, and MEK inhibitors suppressed the tumor growth and NI of SACC cells in nude mice. CONCLUSION: It was identified that inhibitors of EGFR, PI3K/AKT or MEK/ERK suppressed the proliferation, migration, and NI of SACC-83 cells via downregulation of the PI3K/AKT or MEK/ERK pathways. It was also demonstrated that inhibition of EGFR abolishes EMT in SACC by inhibiting the signaling of PI3K/AKT and MEK/ERK. The present results suggest the potential effectiveness of targeting multiple oncogenes associated with downstream pathways of EGF/EGFR, as well as potential therapeutic targets to limit NI in SACC by PI3K/AKT or MEK/ERK inhibition.

Bi-level artificial intelligence model for risk classification of acute respiratory diseases based on Chinese clinical data.

OBJECTIVE: The high incidence of respiratory diseases has dramatically increased the medical burden under the COVID-19 pandemic in the year 2020. It is of considerable significance to utilize a new generation of information technology to improve the artificial intelligence level of respiratory disease diagnosis. METHODS: Based on the semi-structured data of Chinese Electronic Medical Records (CEMRs) from the China Hospital Pharmacovigilance System, this paper proposed a bi-level artificial intelligence model for the risk classification of acute respiratory diseases. It includes two levels. The first level is a dedicated design of the "BiLSTM+Dilated Convolution+3D Attention+CRF" deep learning model that is used for Chinese Clinical Named Entity Recognition (CCNER) to extract valuable information from the unstructured data in the CEMRs. Incorporating the transfer learning and semi-supervised learning technique into the proposed deep learning model achieves higher accuracy and efficiency in the CCNER task than the popular "Bert+BiLSTM+CRF" approach. Combining the extracted entity data with other structured data in the CEMRs, the second level is a customized XGBoost to realize the risk classification of acute respiratory diseases. RESULTS: The empirical study shows that the proposed model could provide practical technical support for improving diagnostic accuracy. CONCLUSION: Our study provides a proof-of-concept for implementing a hybrid artificial intelligence-based system as a tool to aid clinicians in tackling CEMR data and enhancing the diagnostic evaluation under diagnostic uncertainty.

[Arthroscopic debridement combined with platelet-rich plasma injection for the treatment of Kellgren-Lawrence gradeâ -â ¢ knee osteoarthritis].

OBJECTIVE: To explore clinical effect of arthroscopic debridement combined with platelet-rich plasma (PRP) injection for Kellgren-Lawrence(K-L) gradeⅠ-Ⅲ knee osteoarthritis (KOA) . METHODS: Totally 117 patients with KOA who underwent arthroscopic debridement combined with injection from November 2015 to January 2019 were retrospectively analyzed. According to different injection drugs, the patients were divided into sodium hyaluronate group(group A) and PRP group(group B). In group A, there were 60 patients, including 27 males and 33 females, aged from 49 to 67 years old with an average age of (54.1±4.8) years old;12 patients with gradeⅠ, 23 patients with gradeⅡand 25 patients with grade Ⅲ according to K-L clssification, 2 ml(20 g) sodium hyaluronate was injected into knee joint after intraoperative, 1, 2, 3 weeks after operation for 4 times. In group B, there were 57 patients, including 25 males and 32 females, aged from 47 to 70 years old with an average of (55.8±5.0) years old, 10 patients with gradeⅠ, 20 patients with gradeⅡand 27 patients with grade Ⅲ according to K-L classification, injected 5 ml PRP at the same time. Postoperative complications was recorded between two groups. Postoperative visual analogue scale(VAS) and Lysholm score at 3, 6, 12 months were used to evaluate improvement of knee pain and joint function. RESULTS: All patients were followed up for 12 to 19 months with an average of (14.1±1.6) months. There was no significant difference in postopertaive complications between group A and group B (P>0.05). Postoperative VAS score in group A at 3, 6, 12 months were 3.0±0.8, 2.0±0.8, 2.6±0.9 respectively, and 2.9±0.8, 1.9±0.7, 2.2±0.8 in group B respectively; and no differnece at 3 and 6 months after operation between two groups (P<0.05), while VAS score in group B was higher than group A at 12 months after operation(P<0.05). Postoperative Lysholm score in group A at 1, 6, 12 months (86.6±1.8, 93.1±2.0, 86.7±1.7) were lower than group B(88.9±1.9, 95.0±2.0, 89.0±1.9)(P<0.05). CONCLUSION: Arthroscopic debridement combined with sodium hyaluronate or PRP injection for K-L gradeⅠ-Ⅲ KOA could effectively relieve pain and improve joint function with higher safety in short term, but the medium-long-term effect of PRP injection is stable.

A hybrid magnet based scanning tunneling microscope.

In this paper, a scanning tunneling microscope (STM) is presented that operates in a 27.5 T magnetic field within a hybrid magnet. The coarse approach of the STM is realized by using an inertial piezoelectric motor, and the scanning is realized by using a miniature scanner, which stands alone on a sapphire base. A combined vibration isolation system consisting of a brick-rubber-brick stack and two springs is used to isolate the vibration generated from the magnet. An enclosed copper shield is used to prevent sound from entering the tip-sample junction. The sound and vibration isolation measures highly improve the stability of the STM imaging. All the materials selected to construct the STM head are nonmagnetic. The drift rates of the STM in the X-Y plane and Z direction are as low as 26.2 pm/min and 34.6 pm/min, respectively, under ambient conditions. The high performance of the homebuilt STM was demonstrated by graphite hexagonal lattice images obtained in magnet fields ranging from 0 T to 27.5 T even without the protection of a vacuum and low temperatures. As far as known, this is the first STM that operates in a hybrid magnet. It is also the first STM that can obtain graphite hexagonal lattice images in magnetic fields up to 27.5 T. Our results greatly contribute to the further STM studies under ambient conditions and ultrahigh magnetic fields.

Pristine S,N-containing Mn-based metal organic framework nanorods enable efficient oxygen reduction electrocatalysis.

Owing to their unique physicochemical properties, metal-organic frameworks (MOFs) are a kind of promising material for electrocatalysis. However, many reports focus on the use of MOFs as precursors to produce efficient electrocatalysts by pyrolysis. The use of pristine MOFs with well-defined structures as efficient electrocatalysts directly is still a challenging problem. Herein, S,N-containing MnII[(Tdc)(4,4'-Bpy)]n with different morphologies have been obtained by using MnII, thiophene-2,5-dicarboxylate (Tdc) and 4,4'-bipyridine (4,4'-Bpy) as raw materials via hydrothermal synthesis. Furthermore, the influences of different hydrothermal reaction times (0, 2 and 4 h) and anions (SO42-, Cl-, NO3- and CH3COO-) on the morphologies, compositions and ORR activity of the resultant Mn-MOFs are also investigated at length. The results indicate that only the reaction of MnSO4 with Tdc and 4,4'-Bpy for 4 h can form relatively uniform one-dimensional (1D) MOF nanorods. The 1D nanorods combine the favorable features towards the oxygen reduction reaction (ORR), such as a high surface area and efficient 1D electron/mass transport capability. Therefore, the MnII[(Tdc)(4,4'-Bpy)]n nanorods display the highest ORR activity with an onset potential of 0.98 V and a half-wave potential of 0.78 V vs. RHE (reversible hydrogen electrode), which is even comparable to that of Pt/C. In addition, the MnII[(Tdc)(4,4'-Bpy)]n nanorods exhibit higher stability, methanol resistance and ORR selectivity than Pt/C. The present study illustrates an efficient fabrication strategy for highly efficient 1D MOF nanorods for energy storage and conversion applications.

CRNDE promotes cell tongue squamous cell carcinoma cell growth and invasion through suppressing miR-384.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is an aggressive head and neck malignancy. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in diverse biological cell processes, such as cell development, fate decisions, cell differentiation, cell migration, and invasion. In our study, we showed that long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) expression was upregulated in TSCC cell lines and tissues. Overexpression of CRNDE increased the TSCC cell proliferation, cell cycle, and cell invasion. Moreover, ectopic expression of CRNDE inhibited the miR-384 expression in the SCC1 cell and increased the Kirsten Ras (KRAS), cell division cycle 42, and insulin receptor substrate 1 expression, which were the direct target genes of miR-384. We demonstrated that the miR-384 expression was downregulated in the TSCC samples compared with the paired adjacent nontumor samples. The expression of CRNDE was negatively correlated with the expression of miR-384 in the TSCC samples. Overexpression of miR-384 suppressed TSCC cell proliferation, cell cycle, and invasion. Furthermore, we demonstrated that CRNDE promoted TSCC cell proliferation and invasion through inhibiting miR-384 expression. These results suggested that CRNDE acts as an oncogene in the development of TSCC, which partially occurs through inhibiting miR-384 expression.

Formation Mechanism and Cohesive Energy Analysis of Metal-Coated Graphene Nanocomposites Using In-Situ Co-Reduction Method.

Nanocomposite powders based on metal-coated graphene were synthesized using an in-situ co-reduction method in order to improve wettability and interfacial bonding between graphene and metal. Graphene oxide (GO) of 2~3 atomic layers was synthesized using the Hummer's method with graphite as a raw material and then dispersed into a dispersing agent solution mixed with N-Methyl pyrrolidone and deionized water to form a homogeneous GO suspension, which was finally added into electroless plating solutions for the reduction process. Copper-coated graphene (Cu@graphene) and nickel-coated graphene (Ni@graphene) were synthesized using this one-step and co-reduction method by mixing salt solutions containing metal ions and GOs into the plating solution. The Cu ions or Ni ions were adsorbed and bonded onto the edges and surfaces of graphene, which was reduced from the GOs using a strong reducing agent of ascorbic acid or sodium borohydride. Crystalline Cu particles with an average size of about 200 nm were formed on the surface of graphene, whereas amorphous or nanocrystalline Ni particles with an average size of 55 nm were formed on the surface of graphene. Distribution of these metal particles on the graphene is homogeneous and highly dispersed, which can effectively improve the sinterability of composite powders. Cohesive energy distribution between graphene and metal interface was analyzed using first-principle calculation method. Formation mechanism of metal coated graphene was identified to be that both the GO and metal ions were simultaneously reduced in the reducing agents and thus a chemical bonding of graphene/metal was formed between the metal particles and graphene.

A novel S-nitrosocaptopril monohydrate for pulmonary arterial hypertension: H2O and -SNO intermolecular stabilization chemistry.

S-nitrosocaptopril (CapNO) possesses dual capacities of both Captopril and an NO donor with enhanced efficacy and reduced side effects. CapNO crystals are difficult to make due to its unstable S-NO bond. Here, we report a novel stable S-nitrosocaptopril monohydrate (CapNO·H2O) that is stabilized by intermolecular five-membered structure, where one H of H2O forms a hydrogen bond with O- of the stable resonance zwitterion Cap-S+=N-O-, and the O in H2O forms the dipole-dipole interaction with S+ through two unpaired electrons. With the chelation and common ion effect, we synthesized and characterized CapNO·H2O that is stable at 4 °C for 180 days and thereafter without significant degradation. Compared to Captopril, CapNO showed direct vasorelaxation and beneficial effect on PAH rats, and could be self-assembled in rat stomach when Captopril and NaNO2 were given separately. This novel CapNO·H2O with low entropy paves an avenue for its clinical trials and commercialization.

Active pharmacovigilance in China: recent development and future perspectives.

BACKGROUND: The effectiveness of active pharmacovigilance depends on the specific methods adopted and the work patterns put into place. Over the past few years, much attention has been paid to the importance of implementing such systems in China. However, less has been done to evaluate the state of implementation and future needs of such systems. METHODS: This paper reviews China's recent approaches to active pharmacovigilance by examining: (1) information collected from scientific articles and the websites of the China Food and Drug Administration and the China National Center for Adverse Drug Reaction Monitoring, (2) information available on China's spontaneous reporting systems (SRS) and active pharmacovigilance system, and (3) annual reports and internal reports on this subject. RESULTS: Areas that improved most meaningfully for China's active pharmacovigilance in recent years appear to include: (1) quicker reporting and more intelligent scanning methods for adverse drug reactions (ADRs), (2) the use of pharmacovigilance approaches to mine electronic hospital records, and (3) the development of integrated systems including the China Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program. CONCLUSION: Not only has the national online SRS system provided a platform for passive pharmacovigilance, it has also become an important platform for various explorations of active pharmacovigilance in China. Quick reporting and intelligent scanning of ADRs, facilitated by automated ADR detection based on electronic hospital records, have accelerated to capabilities for active pharmacovigilance. The outcomes of the programs, such as the China Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program, usher in a new era for China's active pharmacovigilance. These are particularly important to bridge the information system of sentinel hospitals and ADR research centers, but gaps remain. Thus, much work needs to be done before a high-level active pharmacovigilance system is sufficiently mature to ensure drug safety in the country.

Superconducting-Magnet-Based Faraday Rotation Spectrometer for Real Time in Situ Measurement of OH Radicals at 106 Molecule/cm3 Level in an Atmospheric Simulation Chamber.

Atmospheric simulation chambers play vital roles in the validation of chemical mechanisms and act as a bridge between field measurements and modeling. Chambers operating at atmospheric levels of OH radicals (106-107 molecule/cm3) can significantly enhance the possibility for investigating the discrepancies between the observation and model predications. However, few chambers can directly detect chamber OH radicals at ambient levels. In this paper, we report on the first combination of a superconducting magnet with midinfrared Faraday rotation spectroscopy (FRS) for real time in situ measurement of the OH concentration in an atmospheric simulation chamber. With the use of a multipass enhanced FRS, a detection limit of 3.2 × 106 OH/cm3 (2σ, 4 s) was achieved with an absorption path length of 108 m. The developed FRS system provided a unique, self-calibrated analytical instrument for in situ direct measurement of chamber OH concentration.

Pharmacokinetic differences of mifepristone between sexes in animals.

Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes. Mifepristone in plasma or incubation liquid was recovered by liquid-liquid extraction using 1 mL of ethyl acetate. Chromatographic separation was performed on a C18 column at 35 °C, with a gradient elution consisting of methanol and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. And pharmacokinetic parameters such as elimination half-life, and mean residence time were calculated by using the non-compartmental pharmacokinetics data analysis software. In this work, administrations of mifepristone to rats and beagle dogs revealed that the plasma concentrations of mifepristone (AUC, Cmax) were significantly higher (P < 0.05) in females than that in males. In vitro liver microsomal incubation experiments showed that the metabolic rate of mifepristone in males was higher than that in females, which was consistent with the results of in vivo experiments. In general, we first found the sex-related differences about pharmacokinetic properties of mifepristone and revealed the metabolism difference of hepatic microsomal enzyme is the main reason.

Sex-related pharmacokinetic differences and mechanisms of metapristone (RU486 metabolite).

Metapristone is the primary metabolite of the abortifacient mifepristone (RU486), and is being developed as a safe and effective cancer metastatic chemopreventive agent for both sexes. Here, we systematically investigated the sex-related pharmacokinetics of metapristone in both rats and dogs, and explored the related mechanisms of actions. Administration of metapristone to rats and dogs showed that plasma concentrations of metapristone (AUC, C max ) were significantly higher in female dogs and rats than in males. The sex-related differences in pharmacokinetics become more significant after ten consecutive days of oral administration. Female liver microsomes metabolized metapristone significantly slower than the male ones. The results from P450 reaction phenotyping using recombinant cDNA-expressed human CYPs in conjunction with specific CYP inhibitors suggested that CYP1A2 and CYP3A4 are the predominant CYPs involved in the metapristone metabolism, which were further confirmed by the enhanced protein levels of CYP1A2 and CYP3A4 induced by 1-week oral administration of metapristone to rats. The highest tissue concentration of metapristone was found in the liver. The study demonstrates, for the first time, the sex-related pharmacokinetics of metapristone, and reveals that activities of liver microsomal CYP1A2 and CYP3A4 as well as the renal clearance are primarily responsible for the sex-related pharmacokinetics.

Synergistic enhancing effect for mechanical and electrical properties of tungsten copper composites using spark plasma infiltrating sintering of copper-coated graphene.

Successful applications of WCu alloys in high voltage electrical switches require their high strength and excellent conductivity. Unfortunately, the strategies for increasing their strength such as doping with fine particles and alloying often significantly decrease their conductivity. In this paper, we developed a new pathway for fabricating WCu alloys using spark plasma infiltrating sintering of copper-coated graphene (Cu@Gr) composite powders. Cu@Gr was found to partially prevent the formation of WC after sintering, and graphene was uniformly distributed on the surfaces of network Cu phases. Electrical conductivity of 38.512 M·S/m, thermal conductivity of 264 W·m-1·K-1 and microhardness of 278 HV were achieved for the sintered WCu composites doped with only 0.8 wt.% Cu@Gr powders, which showed 95.3%, 24.3%, 28% enhancement compared with those from the conventional sintering using the undoped WCu powders.