A rare germline BMP15 missense mutation causes hereditary ovarian immature teratoma in human.

Ovarian immature teratomas (OITs) are malignant tumors originating from the ovarian germ cells that mainly occur during the first 30 y of a female's life. Early age of onset strongly suggests the presence of susceptibility gene mutations for the disease yet to be discovered. Whole exon sequencing was used to screen pathogenic mutations from pedigrees with OITs. A rare missense germline mutation (C262T) in the first exon of the BMP15 gene was identified. In silico calculation suggested that the mutation could impair the formation of mature peptides. In vitro experiments on cell lines confirmed that the mutation caused an 84.7% reduction in the secretion of mature BMP15. Clinical samples from OIT patients also showed a similar pattern of decrease in the BMP15 expression. In the transgenic mouse model, the spontaneous parthenogenetic activation significantly increased in oocytes carrying the T allele. Remarkably, a mouse carrying the T allele developed the phenotype of OIT. Oocyte-specific RNA sequencing revealed that abnormal activation of the H-Ras/MAPK pathway might contribute to the development of OIT. BMP15 was identified as a pathogenic gene for OIT which improved our understanding of the etiology of OIT and provided a potential biomarker for genetic screening of this disorder.

Tuning the Phase Composition of Metal-Organic Framework Membranes for Helium Separation through Incorporation of Fullerenes.

Metal-organic framework (MOF) membranes have attracted significant research interest in gas separation, but efficient helium (He) separation remains a challenge due to the weak polarizability of He and the intrinsic pore size flexibility of MOFs. Herein, incorporated fullerenes (C60 and C70) were used to tune the crystallographic phase composition of ZIF-8 membranes, thus creating small and fixed apertures for selective He permeation. The fullerene-modified ZIF-8 (C60@ZIF-8 and C70@ZIF-8) membranes contain about 20% of the rigid-lattice ZIF-8_I-43m phase and have been prepared as 200-350 nm thick supported layers through electrochemical synthesis. They show a significantly enhanced molecular sieving for He/N2,CH4 together with a satisfactory He permeance of >200 GPU. Specifically, the He/N2 selectivity of the C70@ZIF-8 membrane is up to 30.4, which is much higher than that of the fullerene-free ZIF-8 membrane (5.1) and nearly an order of magnitude higher than those of other reported He-selective MOF membranes. A continuous long-term gas permeation test over 780 h under dry and humid conditions proved the excellent stability of the fullerene-modified ZIF-8 membranes. The general validity and versatility of the proposed strategy for MOF membrane preparation are also demonstrated by the enhancement of the separation performance of a fullerene-modified ZIF-76 membrane.

Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.

PURPOSE: Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. METHODS: A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. RESULTS: A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. CONCLUSIONS: AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

Stretchable, Electrochemically-Stable Electrochromic Devices Based on Semi-Embedded Ag@Au Nanowire Network.

Stretchable electrochromic (EC) devices that can adapt the irregular and dynamic human surfaces show promising applications in wearable display, adaptive camouflage, and visual sensation. However, challenges exist in lacking transparent conductive electrodes with both tensile and electrochemical stability to assemble the complex device structure and endure harsh electrochemical redox reactions. Herein, a wrinkled, semi-embedded Ag@Au nanowire (NW) networks are constructed on elastomer substrates to fabricate stretchable, electrochemically-stable conductive electrodes. The stretchable EC devices are then fabricated by sandwiching a viologen-based gel electrolyte between two conductive electrodes with the semi-embedded Ag@Au NW network. Because the inert Au layer inhibits the oxidation of Ag NWs, the EC device exhibits much more stable color changes between yellow and green than those with pure Ag NW networks. In addition, since the wrinkled semi-embedded structure is deformable and reversibly stretched without serious fractures, the EC devices still maintain excellent color-changing stability under 40% stretching/releasing cycles.

Multiple rib and vertebral fractures associated with Bordetella pertussis infection: a case report.

BACKGROUND: Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis, characterized by paroxysms of severe coughing, and predominantly affects children. We report the first case of multiple fractures in the ribs, lumbar spine, and sacrum associated with severe coughing caused by Bordetella pertussis infection in an adult. CASE PRESENTATION: A 49-year-old female presented with acute-onset chest wall pain for 3 weeks. Imaging results revealed multiple fractures in the ribs and vertebrae, as well as bilateral pleural effusion, pericardial effusion, right pneumothorax, and enlargement of the left parapharyngeal and subclavian lymph nodes. The patient's bone density scan, autoimmune antibodies, bone marrow biopsy, and sacral bone biopsy all came back normal. Imaging test results found no evidence of solid tumors or active TB infection. The patient later recalled having violent coughing prior to the onset of chest pain and several family members having similar symptoms. Her blood sample was sent to the CDC, revealing Bordetella pertussis toxin (PT) IgG titer of 110.68 IU/mL. The patient was diagnosed with pertussis and multiple stress fractures from violent coughing. Symptomatic treatments were administered, and the patient's symptoms improved. The patient was followed up 8 weeks later, she reported no more coughing or chest pain. CONCLUSIONS: Pertussis is not just a pediatric disease, but diagnosis in adults is challenging as patients may present with a myriad of confusing symptoms, such as multiple stress fractures due to violent coughing. Medical and epidemiological histories are key to reaching the correct diagnosis, which is essential for appropriate treatments to avoid further complications. Adult immunization should be suggested both for the protection of the adult population and to prevent transmission to children.

Membrane Life Cycle Management: An Exciting Opportunity for Advancing the Sustainability Features of Membrane Separations.

Membrane science and technology is growing rapidly worldwide and continues to play an increasingly important role in diverse fields by offering high separation efficiency with low energy consumption. Membranes have also shown great promise for "green" separation. A majority of the investigations in the field are devoted to the membrane fabrication and modification with the ultimate goals of enhancing the properties and separation performance of membranes. However, less attention has been paid to membrane life cycle management, particularly at the end of service. This is becoming very important, especially taking into account the trends toward sustainable development and carbon neutrality. On the contrary, this can be a great opportunity considering the large variety of membrane processes, especially in terms of the size and capacity of plants in operation. This work aims to highlight the prominent aspects that govern membrane life cycle management with special attention to life cycle assessment (LCA). While fabrication, application, and recycling are the three key aspects of LCA, we focus here on membrane (module) recycling at the end of life by elucidating the relevant aspects, potential criteria, and strategies that effectively contribute to the achievement of green development and sustainability goals.

Health Status Recognition Method for Rotating Machinery Based on Multi-Scale Hybrid Features and Improved Convolutional Neural Networks.

Rotating machinery is susceptible to harsh environmental interference, and fault signal features are challenging to extract, leading to difficulties in health status recognition. This paper proposes multi-scale hybrid features and improved convolutional neural networks (MSCCNN) health status identification methods for rotating machinery. Firstly, the rotating machinery vibration signal is decomposed into intrinsic modal components (IMF) using empirical wavelet decomposition, and multi-scale hybrid feature sets are constructed by simultaneously extracting time-domain, frequency-domain and time-frequency-domain features based on the original vibration signal and the intrinsic modal components it decomposes. Secondly, using correlation coefficients to select features sensitive to degradation, construct rotating machinery health indicators based on kernel principal component analysis and complete health state classification. Finally, a convolutional neural network model (MSCCNN) incorporating multi-scale convolution and hybrid attention mechanism modules is developed for health state identification of rotating machinery, and an improved custom loss function is applied to improve the superiority and generalization ability of the model. The bearing degradation data set of Xi'an Jiaotong University is used to verify the effectiveness of the model. The recognition accuracy of the model is 98.22%, which is 5.83%, 3.30%, 2.29%, 1.52%, and 4.31% higher than that of SVM, CNN, CNN + CBAM, MSCNN, and MSCCNN + conventional features, respectively. The PHM2012 challenge dataset is used to increase the number of samples to validate the model effectiveness, and the model recognition accuracy is 97.67%, which is 5.63%, 1.88%, 1.36%, 1.49%, and 3.69% higher compared to SVM, CNN, CNN + CBAM, MSCNN, and MSCCNN + conventional features methods, respectively. The MSCCNN model recognition accuracy is 98.67% when validated on the degraded dataset of the reducer platform.

Ultra-Fast Preparation of Large-Area Graphdiyne-Based Membranes via Alkynylated Surface-Modification for Nanofiltration.

Graphdiynes (GDYs), two-dimensional graphene-like carbon systems, are considered as potential advanced membrane material due to their unique physicochemical features. Nevertheless, the scale-up of integrated GDY membranes is technologically challenging, and most studies remain at the theoretical stage. Herein, we report a simple and efficient alkynylated surface-mediated strategy to prepare hydrogen-substituted graphdiyne (HsGDY) membranes on commercial alumina tubes. Surface alkynylation initiates an accelerated surface-confined coupling reaction in the presence of a copper catalyst and facilitates the nanoscale epitaxial lateral growth of HsGDY. A continuous and ultra-thin HsGDY membrane (∼100 nm) can be produced within 15 min. The resulting membranes exhibit outstanding molecular sieving together with excellent water permeances (ca. 1100 L m-2 h-1 MPa-1 ), and show a long-term durability in cross-flow nanofiltration, owing to the superhydrophilic surface and hydrophobic pore walls.

Electrochemical Actuators with Multicolor Changes and Multidirectional Actuation.

Electrochemical (EC) actuators have garnered significant attention in recent years, yet there are still some critical challenges to limit their application range, such as responsive time, multifunctionality, and actuating direction. Herein, an EC actuator with a back-to-back structure is fabricated by stacking two membranes with bilayer V2 O5 nanowires/single-walled carbon nanotubes (V2 O5 NWs/SWCNTs) networks, and shows a synchronous high actuation amplitude (about ±9.7 mm, ±28.4°) and multiple color changes. In this back-to-back structure, the inactive SWCNTs layer is used as a conductive current collector, and the bilayer network is attached to a porous polymer membrane. The dual-responsive processes of V2 O5 nanowires (V2 O5 NWs) actuation films and actuators are also deeply investigated through in situ EC X-ray diffraction and Raman spectroscopy. The results show that the EC actuation of the V2 O5 NWs/SWCNTs film is highly related to the redox behavior of the pseudocapacitive V2 O5 NWs layer. At last, both V2 O5 NWs and W18 O49 nanowires (W18 O49 NWs)-based EC actuators are constructed to demonstrate the multicolor changes and multidirectional actuation induced by the opposite lattice changes of V2 O5 NWs and W18 O49 NWs during ionic de-/intercalation, guiding the design of multifunctional EC actuators in the future.

Rational design of efficient deep eutectic solvents for HCl absorption through their competitive H-bonding interactions.

The design of an efficient absorbent is the premise for recovery and resource utilization of hydrogen chloride (HCl) from its industrial tail gases. Herein, a series of 1-butyl-3-methylimidazolium chloride (BmimCl) based-deep eutectic solvents (DESs) were designed and the solubility behavior for HCl was studied in terms of their structure, basicity, free volume, intermolecular interaction energy, and absorption enthalpy. The relationship between the interaction energy and the phase change in the HCl dissolution process was explored in detail. BmimCl-TAA (thioacetamide) (1 : 1) shows high reversible solubility due to its high free volume, suitable absorption enthalpy, and closer H-bonding (HB) interactions between BmimCl and TAA or HCl. The dissolution mechanism of HCl and the dynamic evolution of the HB network were verified by FT-IR and NMR spectra and quantum chemical calculations. The results show that it is the competitive HB interaction that promotes the dissolution of HCl, reduces the absorption enthalpy, and renders a reversible absorption. Compared with BmimCl, the absorption enthalpy of HCl in BmimCl-TAA (1 : 1) is reduced by 25% and the reversible solubility increased 150%. The reversible solubility of HCl in BmimCl-TAA (1 : 1) is as high as 0.51 g g-1 (1.76 mol mol-1) at 303.15 K and 101.3 kPa, and the absorbent can be regenerated facilely by heating under reduced pressure. This work provides new insights into the rational design of DES for efficient and reversible absorption of HCl and other polar gases.

Interpretable machine learning model to predict rupture of small intracranial aneurysms and facilitate clinical decision.

Estimating whether to treat the rupture risk of small intracranial aneurysms (IAs) with size ≤ 7 mm in diameter is difficult but crucial. We aimed to construct and externally validate a convenient machine learning (ML) model for assessing the rupture risk of small IAs. One thousand four patients with small IAs recruited from two hospitals were included in our retrospective research. The patients at hospital 1 were stratified into training (70%) and internal validation set (30%) randomly, and the patients at hospital 2 were used for external validation. We selected predictive features using the least absolute shrinkage and selection operator (LASSO) method and constructed five ML models applying diverse algorithms including random forest classifier (RFC), categorical boosting (CatBoost), support vector machine (SVM) with linear kernel, light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best ML model. The training, internal, and external validation cohorts included 658, 282, and 64 IAs, respectively. The best performance was presented by SVM as AUC of 0.817 in the internal [95% confidence interval (CI), 0.769-0.866] and 0.893 in the external (95% CI, 0.808-0.979) validation cohorts, which overperformed compared with the PHASES score significantly (all P < 0.001). SHAP analysis showed maximum size, location, and irregular shape were the top three important features to predict rupture. Our SVM model based on readily accessible features presented satisfying ability of discrimination in predicting the rupture IAs with small size. Morphological parameters made important contributions to prediction result.

U-shape core-offset fiber sensor with submicrostrain resolution over a 35 millistrain range.

Large strain with submicro resolution is essential for steel structural monitoring; however, the fiber base sensors are limited by the glass extension to be less than 1%. Here, we propose a U-shape core-offset fiber sensor including four fiber segments to realize a large strain sensor. Four fiber segments with slight length differences in between are core-offset fused together to achieve U-shape spring-like microstructure fiber for large transverse bending radius. The reflected high-order modes at three silica/air interfaces interfere to give a broad spectrum due to unequal segment length, which enables continuous strain detection over 35 mɛ. The air and glass hybrid structure of the device enables the large bending, and hence compression and tension measurement can be achieved simultaneously. The strain sensitivity is up to 20.75 pm/µÉ› with the strain accuracy of 0.5 µÉ›. This novel, to the best of our knowledge, core-offset fiber has high strain sensitivity and large strain range for compression and tension strain measurement. Furthermore, the proposed strain sensor can be fabricated easily for practical applications where large strain with high strain accuracy is needed.

Three-Dimensional Analysis of the Natural-Organic-Matter Distribution in the Cake Layer to Precisely Reveal Ultrafiltration Fouling Mechanisms.

Cake layer formation is the dominant ultrafiltration membrane fouling mechanism after long-term operation. However, precisely analyzing the cake-layer structure still remains a challenge due to its thinness (micro/nano scale). Herein, based on the excellent depth-resolution and foulant-discrimination of time-of-flight secondary ion mass spectrometry, a three-dimensional analysis of the cake-layer structure caused by natural organic matter was achieved at lower nanoscale for the first time. When humic substances or polysaccharides coexisted with proteins separately, a homogeneous cake layer was formed due to their interactions. Consequently, membrane fouling resistances induced by proteins were reduced by humic substances or polysaccharides, leading to a high flux. However, when humic substances and polysaccharides coexisted, a sandwich-like cake layer was formed owing to the asynchronous deposition based on molecular dynamics simulations. As a result, membrane fouling resistances were superimposed, and the flux was low. Furthermore, it is interesting that cake-layer structures were relatively stable under common UF operating conditions (i.e., concentration and stirring). These findings better elucidate membrane fouling mechanisms of different natural-organic-matter mixtures. Moreover, it is demonstrated that membrane fouling seems lower with a more homogeneous cake layer, and humic substances or polysaccharides play a critical role. Therefore, regulating the cake-layer structure by feed pretreatment scientifically based on proven mechanisms should be an efficient membrane-fouling-control strategy.

Structural transformation and electrochemical properties of a nanosized flower-like R-MnO2 cathode in a sodium battery.

High-energy density and low-cost sodium-ion batteries are being sought to meet increasing energy demand. Here, R-MnO2 is chosen as a cathode material of sodium-ion batteries owing to its low cost and high energy density. The structural transformation from the tunnel R-MnO2 to the layered NaMnO2 and electrochemical properties during the charge/discharge are investigated at the atomic level by combining XRD and related electrochemical experiments. Na≤0.04MnO2 has a tunnel R-MnO2 phase structure, Na≥0.42MnO2 has a layered NaMnO2 phase structure, and Na0.04-0.42MnO2 is their mixed phase. Mn3+ 3d4[t2gß3dz2(1)3dx2-y2(0)] in NaMnO2 loses one 3dz2 electron and the redox couple Mn3+/Mn4+ delivers 206 mA h g-1 during the initial charge. The case that the Fermi energy level difference between R-MnO2 and NaMnO2 is lower than that between the layered Na(12-x)/12MnO2 and NaMnO2 makes the potential plateau of R-MnO2 turning into NaMnO2 lower than that of the layered Na(12-x)/12MnO2 to NaMnO2. This can be confirmed by our experiment from the 1st-2nd voltage capacity profile of R-MnO2 in EC/PC (ethylene carbonate/propylene carbonate) electrolyte. The study would give a new view of the production of sustainable sodium battery cathode materials.

A Method for Parameter Identification of Composite Beam Piezoelectric Energy Harvester.

This paper proposes a parameter identification method for the multiparameter identification study of the linear-arch composite beam piezoelectric energy harvester. According to the voltage response characteristics of the system under short-circuit conditions, the mechanical equation is solved by transient excitation, combined with the backbone curve theory and logarithmic attenuation method, to obtain the system's linear damping, linear stiffness, and nonlinear stiffness. According to the voltage response characteristics of the system under open-circuit conditions, combined with the electrical equations, the system electromechanical coupling coefficient and equivalent capacitance coefficient are obtained; numerical simulation results show that the identification parameters have good accuracy. Finally, an experimental platform was built for verification, and the results show that the method has high accuracy and practicability.

High-Flux Vertically Aligned 2D Covalent Organic Framework Membrane with Enhanced Hydrogen Separation.

In this study, we propose a new concept of vertically aligned 2D covalent organic framework (COF) layers forming a membrane for efficient gas separation on the basis of precise size exclusion. Gas transport takes place through the COF interlayer space (typically 0.3-0.4 nm) rather than through the nanometer-sized pore apertures. Construction of such a unique membrane architecture was implemented via in situ oriented growth of 2D COFs inside a skeleton of vertically aligned CoAl-layered double hydroxide (LDH) nanosheets. The resultant vertical COF-LZU1 membrane exhibits a high H2 permeance of ∼3600 GPU together with a desirable separation selectivity for gas mixtures such as H2/CO2 (31.6) and H2/CH4 (29.5), thus surpassing the 2008 Robeson upper bounds. The universality of this approach was demonstrated by successfully producing two types of high-quality vertical COF membranes with superior performance as well as outstanding running stability.

Incidence of hypertension among persons living with HIV in China: a multicenter cohort study.

BACKGROUND: Life expectancy among persons living with HIV (PLWH) has improved with increasing access to antiretroviral therapy (ART), however incidence of chronic comorbidities has simultaneously increased. No data are available regarding the incidence of hypertension among Chinese PLWH. METHODS: We analyzed data collected from patients enrolled in two prospective longitudinal multicenter studies of PLWH initiating ART in China. Incidence rate of hypertension per 100 person-years (PYs) among PLWH was calculated, and Cox proportional hazards models was used to evaluate the association between incident hypertension and traditional and HIV-associated risk factors. RESULTS: Of 1078 patients included in this analysis, 984 ART-naïve patients were hypertension-free at baseline, and contributed 2337.7 PYs of follow up, with a median follow-up period of 1.8 years (range: 1.2-3.2) after initiation of ART. Incidence of hypertension was 7.6 [95% confidence interval (CI): 6.5-8.7] per 100 PYs. In the Cox regression analysis, incidence of hypertension was positively associated with body mass index [adjusted hazard ratio (aHR) 1.07 (1.01,1.13), p = 0.02] and recent viral load (aHR 1.28, 95% CI:1.08-1.51, p < 0.01), and negatively associated with recent CD4+/CD8+ ratio (aHR 0.14, 95% CI:0.06-0.31, p < 0.001), zidovudine exposure (aHR 0.15, 95% CI: 0.10-0.24, p < 0.001) and tenofovir disoproxil fumarate exposure (aHR 0.13, 95% CI: 0.08-0.21, p < 0.001). CONCLUSIONS: The incidence of hypertension was relatively high among Chinese PLWH initiating ART. Recent low CD4+/CD8+ ratio and detectable HIV viremia were associated with incident hypertension, whereas receipt of ART was associated with reduced risk. Hypertension may be mitigated, in part, by excellent HIV care, including viral suppression with ART. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00872417 registered on 31 March, 2009, and NCT01844297 registered on 1 May, 2013.

Prognostic value of receptor status conversion following neoadjuvant chemotherapy in breast cancer patients: a systematic review and meta-analysis.

Biomarkers of breast cancer such as hormone receptors (HR) and human epidermal growth factor 2 (HER2) can be altered after neoadjuvant chemotherapy (NAC). However, whether the conversion of these receptors affects the prognosis of patients remains to be determined. We sought to evaluate the prognostic value of HR and HER2 receptors before and after NAC and to analyze their clinical implications. Relevant studies were used to calculate the pooled hazard ratios, 95% confidence interval (95% CI). This meta-analysis included eight studies with 2847 patients. Compared to patients with HR+ → +, patients with HR+ → - have shorter disease free survival (DFS) (hazard ratio = 2.64, 95% CI 1.86-3.75) and overall survival (OS) (hazard ratio = 2.99, 95% CI 1.97-4.54). Furthermore, patients with HR- → + tend to achieve better DFS (hazard ratio = 0.83, 95% CI 0.60-1.17) compared to patients with HR- → -. Patients with HR- → + gain better OS (hazard ratio = 0.67, 95% CI 0.46-0.99) compared to patients exhibiting HR- → -. When comparing patients with HER2+ → - to patients with HER2+ → +, patients with HER2+ → - tended to achieve better DFS (hazard ratio = 1.65, 95% CI 1.08-2.53) though results for OS (hazard ratio = 1.16, 95% CI 0.54-2.49) were not statistically significant. Our data strongly support the need for redetection of HR and HER2 receptor status of surgical sample following neoadjuvant therapy. Changes in HR status induced by NAC can be used as a prognostic factor in breast cancer patients for predicting both OS and DFS. HER2 change may also be valuable for predicting prognosis. Further research should explore therapeutic strategies for those presenting receptor status conversion.

Pharmacokinetics and tolerability of cinitapride in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study.

Cinitapride (CIN) is a drug for functional dyspepsia. The purpose of the study was to investigate the pharmacokinetics and tolerability of CIN in healthy Chinese volunteers. A randomized, open-label, single- and multiple-dose study was conducted in 12 healthy volunteers. Three different doses of CIN (1, 2, 4 tablets) were given to six groups in the single-dose study, and one tablet (1 mg) of CIN was administered three times a day in the multiple-dose study. Blood samples were collected at predetermined time intervals after CIN dosing and analyzed by LC-MS/MS. Eleven volunteers completed the study. After single dose, the Cmax and AUC of plasma increased approximately linearly with dosage; no statistically significant differences were found in pharmacokinetic parameters between three dose groups. After multiple doses, there was no significant change in Tmax and t1/2 compared with the results from the single dose. After repeated doses, AUC0-t and AUC0-∞ were increased, while CLz/F slightly decreased. And no differences between male and female. The pharmacokinetic parameters of this study were consistent with study results of non-Chinese subjects. Good tolerability was demonstrated in both single- and multiple-dose studies with dosage range from 1 to 4 mg in healthy Chinese subjects.

Numerical Study on Ultrasonic Guided Waves for the Inspection of Polygonal Drill Pipes.

The polygonal drill pipe is one of the most critical yet weakest part in a high-torque drill machine. The inspection of a polygonal drill pipe to avoid its failure and thus to ensure safe operation of the drilling machine is of great importance. However, the current most frequently used ultrasonic inspection method is time-consuming and inefficient when dealing with a polygonal drill pipe, which is normally up to several meters. There is an urgent need to develop an efficient method to inspect polygonal drill pipes. In this paper, an ultrasonic guided wave technique is proposed to inspect polygonal drill pipes. Dispersion curves of polygonal drill pipes are firstly derived by using the semi-analytical finite element method. The ALID (absorbing layer using increasing damping) technique is applied to eliminate unwanted boundary reflections. The propagation characteristics of ultrasonic guided waves in normal, symmetrically damaged, and asymmetrically damaged polygonal drill pipes are studied. The results have shown that the ultrasonic guided wave technique is a promising and effective method for the inspection of polygonal drill pipes.