PARP inhibitor-related haemorrhages: What does the real-world study say?

BackgroundPARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event.MethodsA pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS).Results725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib.ConclusionRecognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence

Ultra-Narrow-Band Filter Based on High Q Factor in Metallic Nanoslit Arrays

Here we propose a novel high Q ultra-narrow-band filter in the optical regime. Multiple high Q resonances are achieved in ultra-thin metallic nanoslit arrays on stacked low index–high index dielectric (LID–HID) substrate. Based on the cooperative effect of suppressed modes and transmission modes, the high spectral resolution of transmission peaks is obtained. The number and Q factor of transmission peaks can be freely manipulated by a simple combination of the stacked LID–HID. It is demonstrated that the linewidths of the transmission peaks can be reduced down to the extreme limit of 1 nm and the Q factor is up to 700 by optimizing the structure parameter of the three-layer LID–HID. The results provide a theoretical basis to design a multi-band nanophotonic device with a high Q factor and have potential applications in the next generation of high-resolution plasmonic biosensing and filtering

Tea Polyphenols Protect the Mammary Gland of Dairy Cows by Enhancing Antioxidant Capacity and Regulating the TGF-β1/p38/JNK Pathway

Tea polyphenols (TPs) are the main active substances in tea and they have many beneficial effects, such as anti-inflammation, antioxidant, anti-cancer and metabolic regulation effects. The quality of milk is affected by mammary gland diseases and there are substantial economic losses resulting from reduced milk production as a consequence of inflammatory injury of the mammary gland. In this study, transcriptome analysis and molecular biology techniques were used to study the effects of TPs on inflammatory injury of the mammary gland. After intervention with TPs, a total of 2085 differentially expressed genes were identified, including 1189 up-regulated genes and 896 down-regulated genes. GO analysis showed that differentially expressed genes played an important role in proton transmembrane transport, oxidation–reduction reactions and inflammatory response. KEGG enrichment suggested that differential genes were concentrated in the TGF-β pathway and active oxygen metabolism process. Experiments were performed to confirm that TPs increased SOD, CAT, T-AOC and GSH-Px content along with a reduction in MDA. Meanwhile, TPs inhibited the expression of TGF-β1 and reduced the phosphorylation of p38 and JNK. The expression of inflammatory cytokines IL-1β, IL-6 and TNF-α were significantly decreased after intervention with TPs. In summary, all the data indicated that TPs protected the mammary gland by enhancing the antioxidant capacity and down-regulating the TGF-β1/p38/JNK pathway

Design of the MEMS Piezoresistive Electronic Heart Sound Sensor

This paper proposes the electronic heart sound sensor, based on the piezoresistive principle and MEMS (Micro-Electro-Mechanical System) technology. Firstly, according to the characteristics of heart sound detection, the double-beam-block microstructure has been proposed, and the theoretical analysis and finite element method (FEM) simulation have been carried out. Combined with the natural frequency response of the heart sound (20~600 Hz), its structure sizes have been determined. Secondly, the processing technology of the microstructure with the stress concentration grooves has been developed. The material and sizes of the package have been determined by the three-layer medium transmission principle. Lastly, the MEMS piezoresistive electronic heart sound sensor has been tested compared with the 3200-type electronic stethoscope from 3M (São Paulo, MN, USA). The test results show that the heart sound waveform tested by the MEMS electronic heart sound sensor are almost the same as that tested by the 3200-type electronic stethoscope. Moreover, its signal-to-noise ratio is significantly higher. Compared with the traditional stethoscope, the MEMS heart sound sensor can provide the first and second heart sounds containing more abundant information about the lesion. Compared with the 3200-type electronic stethoscope from 3M, it has better performance and lower cost

Application of hot melt extrusion to enhance the dissolution and oral bioavailability of oleanolic acid

The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid (OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion (HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test. The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64 (OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture (PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC (P < 0.05) and Cmax (P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA

The complete chloroplast genome and phylogenetic analysis of Astragalus scaberrimus Bunge 1833

Astragalus scaberrimus Bunge 1833 is a widespread perennial herb in northern China. The plant has white flowers and white hairs on the leaves and stems. To determine the chloroplast genome, total DNA was extracted from a sample and sequenced on the Illumina HiSeq4000 platform. After sequencing, the reads of chloroplast DNA were assembled and annotated via NOVOPlasty and PGA respectively. The chloroplast genome of this plant has a circular form with a length of 123,492 bp, a 34% GC content and IR loss. After annotation, a total of 113 genes were predicted for this cp genome, comprising 79 encoded proteins, 4 rRNAs and 30 tRNAs. The evolutionary history indicates that A. scaberrimus was grouped within Astragalus and formed a clade with Astragalus laxmannii with a 100% BS support value. The complete chloroplast genome can serve as a reference for future studies on molecular biology, evolution, population genetics, taxonomy and resource protection

Application of a GIS-Based Fuzzy Multi-Criteria Evaluation Approach for Wind Farm Site Selection in China

The development and utilization of wind energy has alleviated the problems of energy shortage and environmental pollution; however, it caused many negative impacts due to suboptimal site selections. This study proposes an innovative method integrating Geographic Information System (GIS), fuzzy Analytic Hierarchy Process (FAHP), and fuzzy VI&scaron;ekriterijumsko KOmpromisno Rangiranje (VIKOR) for site selection of wind farms in the Wafangdian region, China. The uncertainties caused by subjective judgments of the stakeholders were tackled by the FAHP method firstly, where weight values of six criteria were identified. Next, the fuzzy VIKOR method and GIS tool were used to generate the Qi value of each location for ranking their appropriate degrees for wind energy development. The results demonstrated that the middle and upper parts of the studied area are suitable for the exploitation of wind energy, while the central and eastern areas are unfavorable. The influences exerted by various weight combinations and climate change on a site suitability assessment were examined. The resulting comparison with existing wind farms reflected the practicability and reliability of the proposed method; the estimation of climate change impacts on site selection provided the suggestion and support of a long-term plan for wind power development, and even the energy structure adjustment scheme adapted to climate change

A novel computing architect in ubiquitous electric IoT

The Internet of things (IOT) has attracted great interest in many applications related to the monitoring and control of physical phenomena. The rapid popularity of Internet of things (IOT) equipment has brought unprecedented pressure to data communication and processing on communication network and central cloud infrastructure. Edge computing, as a potential platform to address such challenges, is facing significant challenges from the tension between resource constrained hardware and low latency applications. In this work, we propose a technical framework to meet the challenges. We suggest that computing and communication resources should be sliced horizontally to form a virtual computing platform to solve the problem of resource shortage

Vertical-scale spatial influence of radial oxygen loss on rhizosphere microbial community in constructed wetland

Complex interactions between plants and microorganisms form the basis of constructed wetlands (CWs) for pollutant removal. In the rhizosphere, radial oxygen loss (ROL) plays a key role in the activity and abundance of functional microorganisms. However, little has been done to explore how ROL would influence the niche differentiation of microbial communities at different vertical spatial scales. We demonstrate that ROL decreases with depth, promoting an oxidation-reduction rhizosphere microecosystem in CWs. The high level of ROL in the upper layer could support the oxygen supply for aerobic bacteria (Haliangium), facilitating the COD (60%) and NH4+-N (50%) removal, whereas the enrichment of denitrifiers (e.g., Hydrogenophaga and Ralstonia) and methanotrophs (Methanobaterium) in the lower layer could stimulate denitrification. The function prediction results further certified that the abundance of genes catalyzing nitrifying and denitrification processes were significantly enhanced in the upper and bottom layers, respectively, which was attributed to the oxygen concentration gradient in the rhizosphere. This study contributes to further unraveling the rhizosphere effect and enables an improved understanding of the decontamination mechanisms of CWs