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Abstract The pharmacokinetics of vancomycin exhibit significant inter-individual variability, particularly among elderly patients. This study aims to develop a predictive model that integrates machine learning with population pharmacokinetics (popPK) to facilitate personalized medication management for this demographic. A retrospective analysis incorporating 33 features, including popPK parameters such as clearance and volume of distribution. A combination of multiple algorithms and Shapley Additive Explanations was utilized for feature selection to identify the most influential factors affecting drug concentrations. The performance of each algorithm with popPK parameters was superior to that without popPK parameters. Our final ensemble model, composed of support vector regression, light gradient boosting machine, and categorical boosting in a 6:3:1 ratio, included 16 optimized features. This model demonstrated superior predictive accuracy compared to models utilizing all features, with testing group metrics including an R2 of 0.656, mean absolute error of 3.458, mean square error of 28.103, absolute accuracy within ± 5 mg/L of 81.82%, and relative accuracy within ± 30% of 76.62%. This study presents a rapid and cost-effective predictive model for estimating vancomycin plasma concentrations in elderly patients. The model offers a valuable tool for clinicians to accurately determine effective plasma concentration ranges and tailor individualized dosing regimens, thereby enhancing therapeutic outcomes and safety.

Anthocyanins are plant secondary metabolites belonging to the polyphenol class of natural water-soluble phytopigments. The accumulation of anthocyanins in different plant tissues can improve plant survival under adverse conditions. In addition, plants with the resulting colorful morphology can be utilized as landscape plants. Triticum boeoticum (syn. Triticum monococcum ssp. aegilopoides, 2n=2x=14, AbAb) serves as a valuable genetic resource for the improvement of its close relative common wheat in terms of enhancing resilience to various biotic and abiotic stresses. In our previous study, the EMS-mutagenized mutant Z2921 with a red glume, stem, and rachis was generated from T. boeoticum G52, which has a green glume, stem, and rachis. In this study, the F1, F2, and F2:3 generations of a cross between mutant-type Z2921 and wild-type G52 were developed. A single recessive gene, tentatively designated RgM4G52, was identified in Z2921 via genetic analysis. Using bulked segregant exome capture sequencing (BSE-Seq) analysis, RgM4G52 was mapped to chromosome 6AL and was flanked by the markers KASP-58 and KASP-26 within a 3.40-cM genetic interval corresponding to 1.71-Mb and 1.61-Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Triticum boeoticum (TA299) reference genomes, respectively, in which seven and four genes related to anthocyanin synthesis development were annotated. Unlike previously reported color morphology-related genes, RgM4G52 is a recessive gene that can simultaneously control the color of glumes, stems, and rachis in wild einkorn. In addition, a synthetic Triticum dicoccum–T. boeoticum amphiploid Syn-ABAb-34, derived from the colchicine treatment of F1 hybrids between tetraploid wheat PI 352367 (T. dicoccum, AABB) and Z2921, expressed the red stems of Z2921. The flanking markers of RgM4G52 developed in this study could be useful for developing additional common wheat lines with red stems, laying the foundation for marker-assisted breeding and the fine mapping of RgM4G52.

Rice is one of the most important staple food crops; however, it is prone to cadmium (Cd) accumulation, which has negative health effects. Therefore, methods to reduce Cd uptake by rice are necessary. At present, there is limited research on the effects of co-application of silicon (Si) and goethite in mitigating Cd stress in rice. Furthermore, the specific mechanisms underlying the effects of their combined application on iron plaque formation in rice roots remain unclear. Therefore, this study analyzed the effects of the combined application of Si and goethite on the biomass, physiological stress indicators, Cd concentration, and iron plaques of rice using hydroponic experiments. The results revealed that co-treatment with both Si and goethite increased the plant height and dry weight, superoxide dismutase and catalase activities, photosynthetic pigment concentration, and root activity. Moreover, this treatment decreased the malondialdehyde concentration, repaired epidermal cells, reduced the Cd concentration in the roots by 57.2 %, and increased the number of iron plaques and Cd concentration by 150.9 % and 266.2 % in the amorphous and crystalline fractions, respectively. The Cd/Fe ratio in amorphous iron plaques also increased. Our findings suggest that goethite serves as a raw material for iron plaque formation, while Si enhances the oxidation capacity of rice roots. The application of a combination of Si and goethite increases the quantity and quality of iron plaques, enhancing its Cd fixation capacity. This study provides theoretical evidence for the effective inhibition of Cd uptake by iron plaques in rice, providing insights into methods for the remediation of Cd contamination.

To improve the wear resistance of the Al-based alloys and extend its application spectrum, graphene nano-platelets (GNPs) reinforced Al–12Si matrix composites were fabricated by laser melting deposition (LMD) technology. The microstructure, wear morphologies and surface roughness were characterized by scanning electron microscopy (SEM), electron back-scattered diffraction (EBSD) setups and 3D confocal microscopy. The microhardness and high-speed reciprocating frictional properties both Al–12Si and GNPs/Al–12Si composites were evaluated. The addition of graphene significantly refines the microstructure and improves the wear resistance of the matrix. The formation of a relatively stable mechanically mixed layer (MML) reduces the contact area between the friction pair material and the wear surface, the wear rate and roughness of the Al–12Si – 0.5 wt% GNP reinforced composites decrease with the increase of sliding speed, and the wear mechanism changes from adhesive wear accompanied by abrasive wear to fatigue wear. Meanwhile, as the load increases, the wear rate and roughness increase. The wear mechanism of the composite changes from abrasive wear to a mixed mode (combination of both adhesive and abrasive). This research not only offers valuable information about the Al–Si-based composites but provides theoretical light on their industrial applications.

The dilemma concerning the trade-off between the strength and ductility of alloys has persistently been a significant problem in engineering applications. Conventional techniques such as grain refinement, severe plastic deformation, and precipitation strengthening usually increase strength at the expense of ductility. High entropy alloys with dual-phase structures, on the other hand, generally display excellent strength-ductility synergy. In this study, we attempted to mix pre-alloyed powders of two distinct phases (body-centered cubic - bcc and face-centered cubic - fcc) to fabricate AlCoCrFeMnNi HEAs with a dual-phase structure by selective laser melting. Furthermore, we investigate the impact of varying heat treatment temperatures (900 °C, 1000 °C, and 1100 °C) on its phase composition, microstructure, and mechanical properties. The results show that with an increase in the heat treatment temperature, the volume of the fcc phase increases gradually and the volume of the bcc phase decreases. The columnar structure in the fcc phase transforms into a cellular structure, and a spinodal decomposition is observed with the bcc phase. As the heat treatment temperature increases, the yield strength decreases while the elongation substantially increases, with the samples heat-treated at 1100 °C showing the best comprehensive properties (yield strength ∼700 MPa, tensile strength ∼950 MPa, and ∼15% ductility).

Abstract Real-time imaging of transient structure of the electronic excited state is fundamentally critical to understand and control ultrafast molecular dynamics. The ejection of electrons from the inner-shell and valence level can lead to the population of different excited states, which trigger manifold ultrafast relaxation processes, however, the accurate imaging of such electronic state-dependent structural evolutions is still lacking. Here, by developing the laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, snapshots of the vibrational wave-packets of the excited (A) and ground states (X) of D2O+ are captured simultaneously with sub-10 picometre and few-femtosecond precision. We visualise that θ DOD and ROD are significantly increased by around 50∘ and 10 pm, respectively, within approximately 8 fs after initial ionisation for the A state, and the ROD further extends 9 pm within 2 fs along the ground state of the dication in the present condition. Moreover, the ROD can stretch more than 50 pm within 5 fs along autoionisation state of dication. The accuracies of the results are limited by the simulations. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards to make a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.

Abstract Neutral H2 formation via intramolecular hydrogen migration in hydrocarbon molecules plays a vital role in many chemical and biological processes. Here, employing cold target recoil ion momentum spectroscopy (COLTRIMS) and pump-probe technique, we find that the non-adiabatic coupling between the ground and excited ionic states of ethane through conical intersection leads to a significantly high yield of neutral H2 fragment. Based on the analysis of fingerprints that are sensitive to orbital symmetry and electronic state energies in the photoelectron momentum distributions, we tag the initial electronic population of both the ground and excited ionic states and determine the branching ratios of H2 formation channel from those two states. Incorporating theoretical simulation, we established the timescale of the H2 formation to be ~1300 fs. We provide a comprehensive characterization of H2 formation in ionic states of ethane mediated by conical intersection and reveals the significance of non-adiabatic coupling dynamics in the intramolecular hydrogen migration.

To avoid the formation of cracks and to improve the forming capability and performance of the AlCoCrFeNi high entropy alloy (HEA), equiatomic CoCrFeNiMn HEA was added into equiatomic AlCoCrFeNi HEA to form a novel AlCoCrFeMnNi HEA. Three different compositions were prepared by the selective laser melting (SLM) technique, and their formability, microstructure, and mechanical properties were analyzed. Results revealed that AlCoCrFeMnNi shows a composite-like dual-phase structure composed of a soft FCC phase and hard BCC (A2/B2) phase. With the decrease of Al, the SLM forming capability is improved. Besides, the volume fraction of the phase and the nano-hardness decreases with decreasing Al content.

Faced-centred cubic nanoparticles-strengthened FeCoNiAlTi system high-entropy alloy (HEA) has demonstrated unique mechanical performance advantages with recently developed HEA alloy compositions. One of the key factors determining the performance of an alloy is the efficient manipulation of precipitation. However, the traditional aging method used to achieve this can be problematic. It is time-consuming and difficult to accurately control the distribution of the precipitated phase, which restricts the development of new, high-performance structural materials. Consequently, researchers have been exploring alternative methods to more precisely and effectively manipulate precipitation in alloys. Here, we have utilized both high-efficiency additive manufacturing processes and a short-term aging process to produce (FeCoNi)85·84Al7·07Ti7.09 high-entropy alloys that exhibit outstanding mechanical properties with an ultimate tensile strength of 1625 MPa, yield strength of 1214 MPa and an elongation to failure of 11.6%. Our findings reveal the formation of L12 and L21 nanoparticles phases after aging treatment, and their contents gradually decrease with increasing aging treatment temperature. And, we introduce two strengthening mechanisms of dislocation strengthening and precipitation strengthening into the alloys, and realized the coexistence of high-density dislocations and precipitated phases, thereby exhibiting excellent comprehensive mechanical properties. This approach represents a promising new direction in the development of high-performance alloys, offering a more efficient and effective means of producing materials with improved properties.

ABSTRACT: Objective: Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name medications, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin. Methods: The pharmacokinetic (PK) parameters (Cmax, AUC0∼24, Tmax, and t1/2), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment; the cumulative fraction of response) calculated by Monte Carlo simulation were investigated. Results: Our results demonstrated that compared with generics, brand-name levofloxacin not only had higher drug content, it also showed higher antimicrobial susceptibility, higher resistance to mutation ability, and higher percentage of each dosage interval wherein plasma concentration of antimicrobial agents exceeded the MPC90 (mutant prevention concentration to prevent the mutation of 90% strains) against various clinical isolates. Although the differences in AUC0∼24 between brand-name levofloxacin and generics were not statistically significant (P > 0.05, F test), Monte Carlo simulation results showed cumulative fraction of response values for PK/PD of brand-name medications were higher than generics. Conclusion: Our results indicated that PK or PD equivalence did not imply therapeutic equivalence; thus, we suggest including PK/PD analysis in the bioequivalence evaluation system, which benefits prediction of clinical outcome with high application value.

Abstract The study of molecular valence electron dynamics and their coupling with nuclear motion is one of the frontiers of ultrafast physics and ultrafast chemistry. With time-resolved strong-field ion momentum spectroscopy, we study electron valence and nucleus wavepacket evolution on a femtosecond timescale. Two orientation-dependent bond-breaks of N2O molecules from the same electronic state are studied, and the influence of orbital hybridization and polarization effect during molecular breaking is analyzed based on the measured time-resolved asymmetric Pzsum distributions, allowing a visual representation of electron localization during the dissociation of molecules into ions and atoms. Comparison of experimental and theoretical results on orientation-dependent dissociation dynamics allows us to understand how nuclear motions evolve during fragmentation and to control ultrafast molecular reactions.

The low yield strength of the equiatomic CoCrFeMnNi high-entropy alloy (HEA) at ambient temperature severely limits its future application as engineering materials. Here, a CoCrFeMnNi HEA with a fully recrystallized structure and an excellent strength-ductility combination was prepared by post-deformation annealing (PDA) process (i.e., 773–1173 K for 2 h) after selective laser melting. The evolution of the microstructures and mechanical properties of the as-printed and PDA-processed samples were systemically studied, while the strengthening mechanism of PDA-processed samples was clarified. The high density of dislocations and anisotropic columnar grains in the as-printed samples improved the rate of stored deformation energy, thus effectively promoting grain refinement during the PDA process. Compared to the average grain size of 21.26 μm of the as-printed sample, the average grain size of the PDA-873 sample was decreased to 1.20 μm after full recrystallization. Especially in the PDA-873 sample, we found a large amount of high angle grain boundaries (HAGBs) (∼98.3%) and twin boundaries (TBs) (∼46.6%). Besides, some Cr and Mn-rich oxide particles also precipitated in the PDA-processed samples. The main strengthening mechanisms of PDA-processed samples can be attributed to grain boundary strengthening. The PDA-873 sample exhibits a high yield strength, which is twice as large as that of the as-printed samples, without sacrificing ductility significantly. The present work provides an effective way to manipulate grain size and precipitates in HEAs.

The initial momentum along laser propagation plays a significant role in the electron dynamics during tunneling ionization. Our study shows that the offset emission angle decreases with increasing lateral momentum. By using three-dimensional strong-field approximation calculations with initial transverse momentum and a Coulomb correction, we accurately reproduce the transverse momentum-dependent angular shifts of Ar, Kr, and Xe atoms. We find that these shifts are attributed to the influence of initial momentum, tunneling exits, and a long-range Coulomb potential during electron propagation. Additionally, we establish a formula to reconstruct the initial transverse momentum from the final transverse momentum. The result may provide another perspective on attosecond angular streaking, which is crucial for understanding the influence of the Coulomb potential on electron motion.

This study is cross-sectional in nature and aims to investigate and track sedentary behavior (SB) and physical activity among student (aged 9–23 years) for seven consecutive days using an accelerometer. It also intends to analyze the current status of the daily activities of students using age and school-segment differences. The study recruits a total of 384 students [age: 14.41 ± 3.52 years; body mass index (BMI): 19.66 ± 3.67] from four schools out of which 180 (46.88%) were male. The study uses the means and standard deviations for statistical analysis and independent sample t-tests to determine gender differences. Analysis of covariance is used to determine whether or not daily SB and physical activity were statistically significant students according to gender and school segment followed by LSD post hoc tests for multiple comparisons. The results demonstrate that students were less physically active [moderate- to vigorous-intensity physical activity (MVPA):60.4 ± 23.48 min/day] and more sedentary (598.47 ± 162.63 min/day). The sedentary time of the students displays an inverted U-trend, and their participation in MVPA exhibits a W-shape. After controlling for BMI, the results of ANCOVA point to a significant school-segment effect (p

Barley is a diagnostic plant that often used in the research of soil pollution by heavy metals, our research explored the detoxification and tolerance mechanism of cadmium(Cd) in barley through pot experiment. We investigated subcellular distribution, chemical forms and oxidative damage of Cd in barley leaves, combing with the transmission electron microscopy and Fourier-transform infrared spectroscopy(FT-IR) to further understand the translocation, transformation characteristics and toxic effect of Cd in cells. The results showed that, the bioaccumulation factors in roots and shoots of barley were ranged of 4.03–7.48 and 0.51–1.30, respectively. Barley reduces the toxic effects by storing Cd in the roots and reducing its transport to the shoots. Compared to the control treatment (0 mg/kg), the percentage of Cd in the cell wall fractions of leaves in 300 mg/kg Cd treatment increased from 34.74 % to 38.41 %; the percentage of the organelle fractions increased from 24.47 % to 56.02 %; and the percentage of soluble fraction decreased from 40.80 % to 5.57 %. We found that 69.13 % of the highly toxic inorganic Cd and water-soluble Cd were converted to less toxic pectates and protein-integrated Cd (50.20 %) and undissolved Cd phosphates (18.93 %). This conversion of Cd was mainly due to its combination with -OH, -NH, -CN, -C-O-C, and -C-O-P groups. Excessive Cd induced a significant (P < 0.05) increase in the levels of peroxidase, malondialdehyde, and cell membrane permeability, which damaged the cell membrane and allowed Cd to enter the organelles. The chloroplasts and mitochondria were destroyed, and eventually the metabolism of intracellular substances was affected, resulting in symptoms of toxicity. Our research provides cellular-scale insight into the mechanisms of Cd tolerance in barley.

PurposeIn principle, intensity-modulated electron therapy (IMET) can be delivered through mechanical scanning, with a robotic arm mounting a linac.Materials and methodsHere is a scanning algorithm to identify the back-and-forth, top-to-bottom (zigzag) pattern scan sequence. The algorithm includes generating beam positions with a uniform resolution according to the applicator size; adopting discrete energies to achieve the depth of 90% dose by compositing energies; selecting energy by locating the target’s distal edge; and employing the energy-by-energy scan strategy for step-and-shoot discrete scanning. After a zigzag scan sequence is obtained, the delivery order of the scan spots is optimized by fast simulated annealing (FSA) to minimize the path length. For algorithm evaluation, scan sequences were generated using the computed tomography data of 10 patients with pancreatic cancer undergoing intraoperative radiotherapy, and the results were compared between the zigzag path and an optimized path. A simple calculation of the treatment delivery time, which comprises the irradiation time, the total robotic arm moving time, the time for energy switch, and the time to stop and restart the beam, was also made.ResultsIn these clinical cases, FSA optimization shortened the path lengths by 12%–43%. Assuming the prescribed dose was 15 Gy, machine dose rate was 15 Gy/s, energy switch time was 2 s, stop and restart beam time was 20 ms, and robotic arm move speed was 50 mm/s, the average delivery time was 124±38 s. The largest reduction in path length yielded an approximately 10% reduction in the delivery time, which can be further reduced by increasing the machine dose rate and the robotic arm speed, decreasing the time for energy switch, and/or developing more efficient algorithms.ConclusionMechanically scanning IMET is potentially feasible and worthy of further exploration.

Background: The purpose of this study is to identify and characterize ocular adverse events (AEs) that are significantly associated with anti-VEGF drugs for treatment of neovascular age-related macular degeneration and compare the differences between each drug, and provide clinical reference.Methods: Ocular AEs submitted to the US Food and Drug Administration were analyzed to map the safety profile of anti-VEGF drugs. The Pharmacovigilance tools used for the quantitative detection of signals were reporting odds ratio and bayesian confidence propagation neural network.Results: A total of 10,608,503 AE reports were retrieved from FAERS, with 20,836 for ranibizumab, 19,107 for aflibercept, and 2,442 for brolucizumab between the reporting period of Q1, 2004 and Q3, 2021. We found and analyzed the different AEs with the strongest signal in each drug—ranibizumab-macular ischaemia (ROR = 205.27, IC-2SD = 3.70), retinal pigment epithelial tear (ROR = 836.54, IC-2SD = 7.19); aflibercept-intraocular pressure increased (ROR = 31.09, IC-2SD = 4.61), endophthalmitis (ROR = 178.27, IC-2SD = 6.70); brolucizumab-retinal vasculitis (ROR = 2930.41, IC-2SD = 7.47) and/or retinal artery occlusion (ROR = 391.11, IC-2SD = 6.10), dry eye (ROR = 12.48, IC-2SD = 2.88).Conclusion: The presence of AEs should bring clinical attention. The use of anti-VEGF drugs should be based on the patient’s underlying or present medical condition to reduce any adverse event associated with the treatment.

Lodging is one of the most important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat does. There are many solid-stemmed varieties, landraces, and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by a suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge for transferring solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of a cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, which was tentatively designated Su-TdDof and suppresses stem solidity, was identified in synthetic hexaploid wheat Syn-SAU-117 by using genetic analysis. By using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29 Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genomes, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study might be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for the breeding of lodging resistance in wheat and further cloning the suppressor gene Su-TdDof.

Aiming at difficult image acquisition and low recognition accuracy of two rice canopy pests, rice stem borer and rice leaf roller, we constructed a GA-Mask R-CNN (Generative Adversarial Based Mask Region Convolutional Neural Network) intelligent recognition model for rice stem borer and rice leaf roller, and we combined it with field monitoring equipment for them. Firstly, based on the biological habits of rice canopy pests, a variety of rice pest collection methods were used to obtain the images of rice stem borer and rice leaf roller pests. Based on different segmentation algorithms, the rice pest images were segmented to extract single pest samples. Secondly, the bug generator based on a generative adversarial network strategy improves the sensitivity of the classification network to the bug information, generates the pest information images in the real environment, and obtains the sample dataset for deep learning through multi-way augmentation. Then, through adding channel attention ECA module in Mask R-CNN and improving the connection of residual blocks in the backbone network ResNet101, the recognition accuracy of the model is improved. Finally, the GA-Mask R-CNN model was tested on a multi-source dataset with an average precision (AP) of 92.71%, recall (R) of 89.28% and a balanced score F1 of 90.96%. The average precision, recall, and balanced score F1 are improved by 7.07, 7.65, and 8.83%, respectively, compared to the original Mask R-CNN. The results show that the GA-Mask R-CNN model performance indexes are all better than the Mask R-CNN, the Faster R-CNN, the SSD, the YOLOv5, and other network models, which can provide technical support for remote intelligent monitoring of rice pests.

As the development of the Internet of Things (IoT) continues, Federated Learning (FL) is gaining popularity as a distributed machine learning framework that does not compromise the data privacy of each participant. However, the data held by enterprises and factories in the IoT often have different distribution properties (Non-IID), leading to poor results in their federated learning. This problem causes clients to forget about global knowledge during their local training phase and then tends to slow convergence and degrades accuracy. In this work, we propose a method named FedRAD, which is based on relational knowledge distillation that further enhances the mining of high-quality global knowledge by local models from a higher-dimensional perspective during their local training phase to better retain global knowledge and avoid forgetting. At the same time, we devise an entropy-wise adaptive weights module (EWAW) to better regulate the proportion of loss in single-sample knowledge distillation versus relational knowledge distillation so that students can weigh losses based on predicted entropy and learn global knowledge more effectively. A series of experiments on CIFAR10 and CIFAR100 show that FedRAD has better performance in terms of convergence speed and classification accuracy compared to other advanced FL methods.

Background and purpose: poly-ADP ribose polymerase (PARP) inhibitors show impressive efficacy in a range of tumors. However, concerns about rare and fatal adverse events, including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have arisen. The aim of this study was to excavate and evaluate the risk of PARP inhibitors causing MDS and AML based on real-world data from two international pharmacovigilance databases.Methods: We analyzed adverse event (AE) reports of four PARP inhibitors (olaparib, niraparib, rucaparib and talazoparib) associated with MDS and AML from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and EudraVigilance (EV) databases between 1 October 2014, and 30 September 2021, including demographic characteristics, fatality and times to onset. Three different data mining algorithms were used to detect the signals of PARP inhibitors associated with MDS and AML.Results: In total, 16,710 and 11,937 PARP inhibitor AE reports were found in the FAERS and EV databases, of which 332 and 349 were associated with MDS and AML, respectively. The median latencies of MDS and AML associated with PARP inhibitors were 211 [interquartile range (IQR) 93.5–491.25] days and 355 (IQR 72.00–483.50) days, respectively. The average fatality rates of MDS and AML caused by the four PARP inhibitors were 39.23 and 45.39%, respectively, in the FAERS database, while those in the EV database were 32.32 and 34.94%, respectively. Based on the criteria used for the three algorithms, a significant disproportionate association was found between PARP inhibitors as a drug class and MDS/AML. Notably, the risk of MDS was much higher than that of AML. Olaparib appeared to have a stronger association with MDS and AML than did other PARP inhibitors.Conclusion: In the real world, PARP inhibitors increase the risk of MDS and AML, which can result in high mortality and tend to occur during long-term use. Our findings provide objective evidence for the postmarketing safety of PARP inhibitors.

To reduce the high pre-weaning mortality rate of new-born piglets crushed by sows, a kind of recognition and evaluation method for sows’ behavior based on the scheme of time-sharing and multiplexing by adopting triaxial acceleration and video sensors at day and night is proposed in this paper. For darker scene at night, random forest classifier with optimal 43-dimensional feature vector subset proposed in this paper is adopted to recognize four kinds of macro behaviors of sows roughly by adopting triaxial acceleration sensor MPU6050. The recognition rate can reach 89.4%. For brighter light scene during the day, an improved bilinear convolutional neural network method based on CBAM module is proposed in this paper to recognize seven kinds of micro behaviors of sows by video sensor. The recognition rate can reach 84.4%. The methods proposed in this paper can meet the requirement of real-time to recognize the behavior of sows during 24 hours on the premise of ensuring accuracy. Finally, an evaluation model of sows’ maternal behavior level is set up in this paper. The achivement of the study can not only help the farm to select sows with higher maternal ability for breeding piglets, but also avoid the large-scale economic losses caused by the high mortality rate of piglets before weaning of the farm.

Abstract Background Graves' disease (GD) is a clinical autoimmune thyroid disease. During the treatment of GD, antithyroid drug‐induced agranulocytosis (TIA) is a common and even life‐threatening adverse drug reaction. Previous studies suggested that susceptibility to TIA is strongly associated with HLA‐B*27:05, HLA‐B*38:02, and HLA‐DRB1*08:03 genetic variation and six single nucleotide polymorphisms (SNPs) in MICA genes. Aims The purpose of this study is to further study the associations between TIA, HLA‐B and MICA. Materials & Methods We genotyped MICA‐STR and MICA‐129 variants in 41 TIA and 308 control patients with GD and investigated the linkage effect among SNPs and short tandem repeat (STR) of MICA and HLA‐B alleles. Results The results showed that MICA*A5.1 was significantly associated with TIA (p = .007, odd ratio = 1.958, 95% confidence interval, 1.192–3.214). In addition, high linkage among MICA‐129 and six SNPs MICA and HLA‐B was detected, and two haplotypes (AAAACAAAAACGGCCTA and AACAAAAAAAACATTAA (p = 5.14E−07 and p = 3.42E−08, respectively)) were significantly associated with TIA. Furthermore, when we analyzed only MICA‐129 and HLA‐B separately, the haplotypes (AAAACAAAAAA with p = 2.49E−07 and AACAAAAAAAA with p = 2.14E−09) were identified with more significant effects. MICA‐129 was completely linked to six SNPs with haplotypes ACATTACA (p = 2.05E−05) significantly associated with TIA. Conclusion These data indicated that there was a significant linkage effect between MICA‐129 and other alleles, suggesting that they exert interactive effects as risk factors for the development of TIA.

ObjectiveTo establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method.MethodsA retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model.ResultsThree algorithms (SVR, GBRT, and RF) with high R2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors.ConclusionWe firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.

PurposeTo explore the feasibility and safety of centrally located hepatocellular carcinoma (CL-HCC) treated by narrow-margin resection combined with intraoperative electron radiotherapy (IOERT).Methods and MaterialsFrom November 2009 to November 2016, 37 consecutive patients were treated with IOERT as adjuvant treatment during narrow-margin resection for CL-HCC. Long-term outcomes, adverse events for surgery, and acute and chronic toxicities were analyzed.ResultsThe median follow-up was 57.82 months (range, 3.75-111.41 months). A total dose of 15 Gy (range 12 to 17Gy) (prescribed at the 90% isodose) was delivered with a 0.9cm (range 0.8-1.2 cm) median treatment depth targeting the narrow-margin. The 1-year, 3-year and 5-year OS rates were 91.39%, 88.34% and 88.34%, respectively. The 1-year, 3-year and 5-year DFS rates were 80.81%, 68.59% and 54.17%, respectively. In the univariate analysis, none of the treatment characteristics were predictive of overall survival. Fifteen (40.5%) patients suffered from a recurrence event. No patient had marginal recurrence. The 1-year, 3-year and 5-year intrahepatic recurrence rates were 19.75%, 25.92% and 39.58%, respectively. The 1-year, 3-year and 5-year extrahepatic recurrence rates were 2.7%, 5.95% and 9.87%, respectively. There was no 30-day surgical-related death. Three patients had grade 4, and 28 patients had grade 3 alanine aminotransferase (ALT) levels, and seven patients had grade 4, and 30 patients had grade 3 aspartate transaminase (AST) levels. All of them returned to normal within four months. There was no acute radiation-induced liver injury during follow-up. There were no acute or chronic toxicities associated with IOERT.ConclusionIOERT for narrow-margin CL-HCC may achieve good long-term survival outcomes, without significantly increasing acute and chronic toxicities. An IOERT dose of 15Gy may be the safest and most feasible. IOERT might be considered as an adjuvant therapy for CL-HCC patients with a narrow-margin.

Diabetic cardiomyopathy (DCM) is one of the main complications of diabetic patients and the major reason for the high prevalence of heart failure in diabetic patients. Fufang Xueshuantong (FXST) is a traditional Chinese medicine formula commonly used in the treatment of diabetic retinopathy and stable angina pectoris. However, the role of FXST in DCM has not yet been clarified. This study was conducted to investigate the effects of FXST on diabetic myocardial lesions and reveal its molecular mechanism. The rats were intraperitoneally injected with 65 mg/kg streptozotocin (STZ) to induce diabetes mellitus (DM). DM rats were given saline or FXST. The rats in the control group were intraperitoneally injected with an equal amount of sodium citrate buffer and gavaged with saline. After 12 weeks, echocardiography, heart weight index (HWI), and myocardial pathological changes were determined. The expression of transforming growth factor-beta1 (TGF-β1), collagen I, and collagen III was examined using immunofluorescence staining and western blot. The expressions of Wnt/β-catenin signaling pathway-related proteins and mRNA were detected by western blot and real-time PCR. The results showed that FXST significantly improved cardiac function, ameliorated histopathological changes, and decreased HWI in the DM rats. FXST significantly inhibited the expression of myocardial TGF-β1, collagen I, and collagen III in DM rats. Furthermore, FXST significantly inhibited the Wnt/β-catenin pathway. Taken together, FXST has a protective effect on DCM, which might be mediated by suppressing the Wnt/β-catenin pathway.

Based on the output data from the Lagrangian flexible particle dispersion model (FLEXPART), we analyze the pathways of moisture to identify the moisture source areas for extreme precipitation in the summer half-year (April–September) over northern and southern Xinjiang, respectively. For both northern and southern Xinjiang, the local evaporation plays a decisive role for extreme precipitation in the summer half-year, of which contribution ratio accounts for 24.5% to northern Xinjiang and 30.2% to southern Xinjiang of all identified source areas. In addition, central Asia and northwestern Asia are the major moisture source areas as well and contribute similarly to extreme precipitation relative to local evaporation. For northern Xinjiang, central Asia surpasses northwestern Asia, and each of them contributes 24.1 and 18.8%, whereas northwestern Asia is somewhat more crucial than central Asia for southern Xinjiang, accounting 22.1 and 19.1%, respectively. Note that the three top-ranked moisture source areas make up a large proportion of total sources. Regarding the remaining source areas that also provide moisture, the contributions are entirely different for southern and northern Xinjiang. Originating from the North Atlantic Ocean, Europe, and the Mediterranean Sea, some water vapor enters northern Xinjiang and converge to precipitate, while this process is barely detectable for extreme precipitation over southern Xinjiang, which is affected by the westerly flow. On the contrary, the Arabian Sea, the Arabian Peninsula, and the Indian Peninsula contribute, even though slightly, to extreme precipitation over southern Xinjiang, which indicates that the meridional transport pathways from the Arabian Sea can carry moisture to this inland region.

Knowledge on the spectral properties of the tautomers of milrinone (MLR) in solvents and solid-state, as well as under light conditions is of critical importance from both theoretical and practical points of view. Herein, we investigated the spectral properties of MLR in different conditions using UV-Vis and fluorescence spectroscopies. The experimental results demonstrated that MLR can undergo the tautomerization reaction induced by solvent polarity, light and pH, eliciting four tautomeric structures (enol, keto, anion, and cation forms). The interesting multi-functional groups in MLR enable it to coordinate with metal ions or to recognize gust molecules by H-bonding. In the use of MLR as an excited-state intermolecular proton transfer (inter-ESPT) fluorescent probe, a highly sensitive and selective analysis of Fe3+ was developed, which offered a sensitive detection of Fe3+ with the detection limit of 3.5 nM. More importantly, MLR exhibited the ability of anchoring proteins and led to the recognition-driven turn-on inter-ESPT process, highlighting the potential for the probe to image proteins in electrophoresis gels. The spectral experimental results revealed the possible degradation mechanism, so that we can better understand the side effects of oral preparations. The use of the available drug as an inter-ESPT fluorescent probe is simple and accurate, providing a good method for Fe3+ ion sensing and protein staining.

PurposeTreatment of multiple brain metastases with single-isocenter volumetric modulated arc therapy causes unnecessary exposure to normal brain tissue. In this study, a longitudinal grouping method was developed to reduce such unnecessary exposure.Materials and MethodsThis method has two main aspects: grouping brain lesions longitudinally according to their longitudinal projection positions in beam’s eye view, and rotating the collimator to 90° to make the multiple leaf collimator leaves conform to the targets longitudinally group by group. For 11 patients with multiple (5–30) brain metastases, two single-isocenter volumetric modulated arc therapy plans were generated using a longitudinal grouping strategy (LGS) and the conventional strategy (CVS). The prescription dose was 52 Gy for 13 fractions. Dose normalization to 100% of the prescription dose in 95% of the planning target volume was adopted. For plan quality comparison, Paddick conformity and the gradient index of the planning target volume, and the mean dose, the V100%, V50%, V25%, and V10% volumes of normal brain tissue were calculated.ResultsThere were no significant differences between the LGS and CVS plans in Paddick conformity (p = 0.374) and the gradient index (p = 0.182) of the combined planning target volumes or for V100% (p = 0.266) and V50% (p = 0.155) of the normal brain. However, the V25% and V10% of the normal brain which represented the low-dose region were significantly reduced in the LGS plans (p = 0.004 and p = 0.003, respectively). Consistently, the mean dose of the entire normal brain was 12.04 and 11.17 Gy in the CVS and LGS plans, respectively, a significant reduction in the LGS plans (p = 0.003).ConclusionsThe longitudinal grouping method can decrease unnecessary exposure and reduces the low-dose range in normal brain tissue.

Abstract Background Troxerutin (TRX), a naturally occurring flavonoid in various fruits, has been reported to exhibit numerous pharmacological and biological activities in vitro and in vivo. However, the molecular mechanisms underlying TRX as a treatment for disease are poorly understood. Methods Using pharmacophore mapping and inverse docking, a set of potential TRX target proteins that have been associated with multiple forms of diseases was obtained. Bioinformatic analyses were performed using the Enrichr and STRING servers to analyse the related biological processes and protein-protein networks. Furthermore, we investigated the potential protective effect of TRX against lipopolysaccharide-induced acute lung injury (ALI) using a mouse model. Morphological changes in the lungs were assessed using haematoxylin and eosin staining. Inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 were investigated using ELISA. Activation of MAPK and NF-κB was detected using western blotting. Results Our network pharmacology analysis revealed the existence of multiple TRX-related chemical-target interactions and the related biological processes. We found that pretreatment with TRX protected against histological changes and obviously regulated the inflammatory cell counts and inflammatory cytokine levels in bronchoalveolar lavage fluid. Based on bioinformatic and western blot analyses, TRX may exert a protective effect against ALI by inhibiting MAPK and NF-κB signalling. Conclusions TRX can ameliorate pulmonary injury by inhibiting the MAPK and NF-κB signalling pathways and has a potential protective effect against ALI. This study may be helpful for understanding the mechanisms underlying TRX action and for discovering new drugs from plants for the treatment of ALI.

Nitrite (NO2−) is a common pollutant and is widely present in the environment and in human bodies. The development of a rapid and accurate method for NO2− detection is always a very important task. Herein, we synthesized a partnered excited-state intermolecular proton transfer (ESIPT) fluorophore using the “multi-component one pot” method, and used this as a probe (ESIPT-F) for sensing NO2−. ESIPT-F exhibited bimodal emission in different solvents because of the solvent-mediated ESIPT reaction. The addition of NO2− caused an obvious change in colors and tautomeric fluorescence due to the graft of NO2− into the ESIPT-F molecules. From this basis, highly sensitive and selective analysis of NO2− was developed using tautomeric emission signaling, achieving sensitive detection of NO2− in the concentration range of 0~45 mM with a detection limit of 12.5 nM. More importantly, ESIPT-F showed the ability to anchor proteins and resulted in a recognition-driven “on-off” ESIPT process, enabling it to become a powerful tool for fluorescence imaging of proteins or protein-based subcellular organelles. MTT experimental results revealed that ESIPT-F is low cytotoxic and has good membrane permeability to cells. Thus, ESIPT-F was further employed to image the tunneling nanotube in vitro HEC-1A cells, displaying high-resolution performance.

We experimentally demonstrate supercontinuum (SC) generation in a germanium-on-silicon waveguide. This waveguide exhibits propagation loss between 1.2 dB/cm and 1.35 dB/cm in the 3.6 µm–4.5 µm spectral region for both transverse electric (TE) and transverse magnetic (TM) polarizations. By pumping the waveguide with ∼200 fs pulses at 4.6 µm wavelength, we generate a mid-infrared (IR) SC spanning nearly an octave from 3.39 µm to 6.02 µm at the −40 dB level. Through numerical analysis of the evolution of the SC, we attribute the current limit to further extension into the mid-IR mainly to free-carrier absorption.

Doxorubicin (DOX) is commonly used as an anti-cancer agent. However, its severe cardiotoxicity often makes it life threatening even long after DOX therapy during childhood. We recently reported interferon-γ (IFN-γ) necessary for DOX-induced acute cardiotoxicity in a p38 dependent way and, asked here for the potential of IFN-γ blockade to prevent DOX-induced chronic cardiotoxicity during tumor therapy. In our model system, mice without or with growing tumors repeatedly received DOX treatment. Simultaneous injection of anti-IFN-γ antibody R46-A2 with DOX to block IFN-γ signal efficiently protected the cardiac function of DOX treated recipients. Importantly, a single late injection of R46-A2 after DOX exposure also ameliorated DOX induced cardiac dysfunction in tumor-bearing mice. The anti-IFN-γ treatment did not affect the DOX-mediated tumor suppression effect and it left the main cellular immune response intact. Therefore, temporary blockade of IFN-γ may represent a novel strategy to ameliorate established DOX induced cardiotoxicity (DIC) or prevent its development in tumor therapy.

The intricately fluctuating onset of respiratory and circulatory diseases displays rhythms of multi-scaled meteorological conditions due to their sensitivity to weather changes. The intrinsic meteorological rhythms of these diseases are revealed in this bio-meteorological study via Fourier decomposition and harmonic analysis. Daily emergency room (ER) visit data for respiratory and circulatory diseases from three comprehensive hospitals in Haidian district of Beijing, China were used in the analysis. Meteorological data included three temperature metrics, relative humidity, sunshine duration, daily mean air pressure, and wind speed. The Fourier decomposition and harmonic analysis on ER visits and meteorological variables involve frequency, period, and power of all harmonics. The results indicated that: i) for respiratory morbidity, a strong climatic annual rhythm responding to annual temperature change was firstly revealed; its ratio of spectral density was 16–33%. Moreover, significant correlations existed between the high-frequency fluctuations (

Impairment of cognitive functions has been reported in prolactinomas. However, the electrophysiological mechanisms of response activation and response inhibition in prolactinomas remain unclear. We recorded participants’ scalp electroencephalography (EEG) in a visual Go/Nogo task. Compared to the healthy controls (HCs), the patients demonstrated worse performance and their prolactin (PRL) levels negatively correlated with behavioral results. Meanwhile, patients’ P300 amplitudes in the Go and Nogo conditions were smaller than the HCs. The amplitudes of N200nogo in patients were smaller than the HCs as well. Lower frontal theta power was found in the patients than the HCs in both Go and Nogo conditions, which indicated a deficit in response activation and inhibition. Moreover, the PRL levels mediated the relationship between frontal theta power and behavior performance, implying that lower frontal theta power caused the dysfunction of response control by abnormally high PRL levels. Patients also showed lower occipital alpha power than the HCs, which suggested that the impaired response inhibition may arise from deficient attention control. Taken together, the present study revealed the neurocognitive discrepancies between prolactinomas and the HCs. The frontal theta oscillation was highlighted as the electrophysiological markers of the impaired response control in prolactinomas.

Constructing excited-state intermolecular proton transfer (ESIPT-e) fluorophores represents significant challenges due to the harsh requirement of bearing a proton donor-acceptor (D-A) system and their matching proton donating-accepting ability in the same molecule. Herein, we synthesized a new-type ESIPT-e fluorophor (2-APC) using the “four-component one-pot” reaction. By the installing of a cyano-group on pyridine scaffold, the proton donating ability of -NH2 was greatly enhanced, enabling 2-APC to undergo ESIPT-e process. Surprisingly, 2-APC exhibited dual-emissions in protic solvents ethanol and normal fluorescence in aprotic solvents, which is vastly different from that of conventional ESIPT-a dyes. The ESIPT emission can be obviously suppressed by Fe3+ due to the coordination reaction of Fe3+ with the A-D system in 2-APC. From this basis, a highly sensitive and selective method was established using 2-APC as a fluorescent probe, which offers the sensitive detection of Fe3+ ranging from 0 to 13 μM with the detection limit of 7.5 nM. The recovery study of spiked Fe3+ measured by the probe showed satisfactory results (97.2103.4%) with the reasonable RSD ranging from 3.1 to 3.8%. Moreover, 2-APC can also exhibit aggregation-induced effect in poor solvent or solid-state, eliciting strong red fluorescence. 2-APC was also applied to cell-imaging, exhibiting good cell-permeability, biocompatibility and color rendering. This multi-mode emission of 2-APC is significant departure from that of conventional extended p-conjugated systems and ESIPT dyes based on a flat and rigid molecular design. The “one-pot synthesis” strategy for the construction of ESIPT molecules pioneered a new route to achieve tricolor-emissive fluorophores.

Abstract Integrated microwave photonics has strongly emerged as a next-generation technology to address limitations of conventional RF electronics for wireless communications. High-resolution RF signal processing still remains a challenge due to limitations in technology that offer sub-GHz spectral resolution, in particular at high carrier frequencies. In this paper, we present an on-chip high-resolution RF signal processor, capable of providing high-suppression spectral filtering, large phase shifts and ns-scale time delays. This was achieved through tailoring of the Brillouin gain profiles using Stokes and anti-Stokes resonances combined with RF interferometry on a low-loss photonic chip with strong opto-acoustic interactions. Using an optical power of

Signal processing using on-chip nonlinear or linear optical effects has shown tremendous potential for RF photonic applications. Combining nonlinear and linear elements on the same photonic chip can further enable advanced functionality and enhanced system performance in a robust and compact form. However, the integration of nonlinear and linear optical signal processing units remains challenging due to the competing and demanding waveguide requirements, specifically the combination of high optical nonlinearity in single-pass waveguides, which is desirable for broadband signal processing with low linear loss and negligible nonlinear distortions required for linear signal processing. Here, we report the first demonstration of integrating Brillouin-active waveguides and passive ring resonators on the same integrated photonic chip, enabling an integrated microwave photonic notch filter with ultradeep stopband suppressions of >40 dB, a low filter passband loss of

Stimulated Brillouin scattering drives a coherent interaction between optical signals and acoustic phonons and can be used for storing optical information in acoustic waves. An important consideration arises when multiple optical frequencies are simultaneously employed in the Brillouin process: in this case, the acoustic phonons that are addressed by each optical wavelength can be separated by frequencies far smaller than the acoustic phonon linewidth, potentially leading to cross talk between the optical modes. Here we extend the concept of Brillouin-based light storage to multiple wavelength channels. We experimentally and theoretically show that the accumulated phase mismatch over the length of the spatially extended phonons allows each optical wavelength channel to address a distinct phonon mode, ensuring negligible cross talk and preserving the coherence, even if the phonons overlap in frequency. This phase-mismatch for broad-bandwidth pulses has far-reaching implications allowing dense wavelength multiplexing in Brillouin-based light storage, multifrequency Brillouin sensing and lasing, parallel microwave processing, and quantum photon-phonon interactions.

Semen abnormality (SA) male infertility has become a worldwide reproductive health problem. The invasive tests (e.g., testicular biopsy) and labor-intensive methods of semen collection severely inhibit diagnosis of male infertility. In addition, the pathogenesis and biological interpretation of male infertility are still obscure. In this report, a total of 84 semen abnormality (SA) patients, diagnosed as teratozoospermia (TE, n = 21), asthenozoospermia (AS, n = 23), oligozoospermia (OL, n = 20), azoospermia (AZ, n = 20), and age-matched healthy controls (HC, n = 29) were analyzed by GC-MS for discrimination analysis and discovery of potential biomarkers. Twenty-three biomarkers were obtained by multivariate statistical method (partial least squares-discriminant analysis, PLS-DA) and univariate statistical method (analysis of variance, ANOVA) with comparisons of TE versus HC, AS versus HC, OL versus HC and AZ versus HC. Based on those biomarkers, the most relevant pathways were mainly associated with the metabolism of carbohydrates, amino acids, and lipids. The principal metabolic alternations in SA male infertility included increased levels of energy-related metabolisms, such as tricarboxylic acid cycle, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine, threonine metabolism and saturated fatty acid metabolism. Furthermore, increased levels of glutathione metabolism were related to oxidative stress. Finally, decreased levels of arginine and proline metabolism and inositol phosphate metabolism were observed. In conclusion, blood plasma metabolomics is powerful for characterizing metabolic disturbances in SA male infertility. From metabolic pathway analysis, energy production, oxidation stress and the released enzyme during spermatogenesis take the primary responsibilities for SA male infertility.

Extruded Al-Zn-Mg-Cu alloy samples with grains aligned parallel to the extrusion direction were subjected to high-pressure annealing. The effects of annealing pressure on the microstructure, hardness, and corrosion properties (evaluated using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS)) were investigated. Phase analysis showed the presence of MgZn2 and α-Al phases, the MgZn2 phase dissolved into the matrix, and its amount decreased with the increasing annealing pressure. The recrystallization was inhibited, and the grains were refined, leading to an increase in the Vickers hardness with increasing the annealing pressure. The corrosion resistance was improved after high-pressure treatment, and a stable passivation layer was observed. Meanwhile, the number of corrosion pits and the width of corrosion cracks decreased in the high-pressure annealed samples.

In this paper, the key technology of interferometric microwave thermometer is studied, the research can be applied to the temperature measurement of human body and subcutaneous tissue. This paper proposes a hardware architecture of interferometric microwave thermometer with 2 GHz bandwidth, in which the phase shifter is used to correct phase error and the quadrature demodulator is used to realize autocorrelation detection function. The results show that when input power is 7 dBm, the detection sensitivity can reach 176.54 mV/dBm and the temperature resolution of the microwave radiometer can reach 0.4 K. Correction algorithm is designed to improve the accuracy of temperature measurement. After correction, the phase error is reduced from 40° to 1.4° and when temperature changes 0.1 °C, the voltage value changes obviously. Step-by-step calibration and overall calibration are used to calibrate the device. Inversion algorithm can determine the relationship between physical temperature and output voltage. The mean square error of water temperature inversion by multiple linear regression algorithm is 0.607 and that of BP neural network algorithm is 0.334. The inversion accuracy can be improved by reducing the temperature range. Our work provides a promising realization of accurate, rapid and non-contact detection device of human body temperature.

The Al-20Si-5Fe-3Cu-1Mg alloy was fabricated using selective laser melting (SLM). The microstructure and properties of the as-prepared SLM, post-treated SLM, and SLM with substrate plate heating are studied. The as-prepared SLM sample shows a non-uniform microstructure with four different phases: fcc-αAl, eutectic Al-Si, Al2MgSi, and δ-Al4FeSi2. With thermal treatment, the phases become coarser and the δ-Al4FeSi2 phase transforms partially to β-Al5FeSi. The sample produced with SLM substrate plate heating shows a relatively uniform microstructure without a distinct difference between hatch overlaps and track cores. Room temperature compression test results show that an as-prepared SLM sample reaches a maximum strength (862 MPa) compared to the heat-treated (524 MPa) and substrate plate heated samples (474 MPa) due to the presence of fine microstructure and the internal stresses. The reduction in strength of the sample produced with substrate plate heating is due to the coarsening of the microstructure, but the plastic deformation shows an improvement (20%). The present observations suggest that substrate plate heating can be effectively employed not only to minimize the internal stresses (by impacting the cooling rate of the process) but can also be used to modulate the mechanical properties in a controlled fashion.

Supercapacitors (SCs), one of the most popular types of energy-storage devices, present lots of advantages, such as large power density and fast charge/discharge capability. Being the promising SCs electrode materials, metal–organic frameworks (MOFs) and their derivatives have gained ever-increasing attention due to their large specific surface area, controllable porous structure and rich diversity. Herein, the recent development of MOFs-based materials and their application in SCs as the electrode are reviewed and summarized. The preparation method, the morphology of the materials and the electrical performance of various MOFs and their derivatives (such as carbon, metal oxide/hydroxide and metal sulfide) are briefly discussed. Most of recent works concentrate on Ni-, Co- and Mn-MOFs and their composites/derivatives. Conclusions and our outlook for the researches are also given, which would be a valuable guideline for the rational design of MOFs materials for SCs in the near future.

BC _5 with both superhard and superconducting properties is expected to have important applications in many fields. In this work, the low-index surface structures and properties of BC _5 have been identified by first-principles calculations. The surface stability decreased in the order of (011) > (010) > (101) > (100) > (110) > (111) > (001). The (011), (101), and (110) surfaces exhibit the strongest surface relaxation, followed by (111), and the (001) surface is the least. A DFT (density functional theory)-based Wulff construction of the equilibrium shape of BC _5 shows that the surface with the largest exposure area is (011), followed by the (101) and (001) surfaces. Electronic analyses show that Pmma phase BC _5 and all considered low-index surfaces exhibit metallic character where the surfaces are even stronger. Larger charge redistribution in the low-index surfaces is found compared with the bulk case.

The preparation of Cu-based coatings on AlN ceramic surface was accomplished by laser cladding and brazing technology. The Cu-based coating was prepared by both copper powder and titanium powder on ceramic surface. The microstructure and properties were tested by x-ray diffraction, metallurgical microscope, scanning electron microscope, energy dispersive spectrometer and microhardness tester. The novelties of this paper in the method of laser cladding and brazing were used to prepare Cu-coating on ceramic surface and the addition of Ti could improve the properties of Cu-based coating. The addition of Ti improved the wettability of ceramic surface. According to the results of EDS, Ti could better get into the Cu-based coating and formed metallurgical bonding in the laser cladding. The microhardness of laser cladding was higher than brazing, which could be concluded that it was due to the rapid cooling rate during the laser cladding could restrain grain growth and element segregation.

The interaction of optical and acoustic waves via stimulated Brillouin scattering (SBS) has recently reached on-chip platforms, which has opened new fields of applications ranging from integrated microwave photonics and on-chip narrow-linewidth lasers, to phonon-based optical delay and signal processing schemes. Since SBS is an effect that scales exponentially with interaction length, on-chip implementation on a short length scale is challenging, requiring carefully designed waveguides with optimized opto-acoustic overlap. In this work, we use the principle of Brillouin optical correlation domain analysis to locally measure the SBS spectrum with high spatial resolution of 800 μm and perform a distributed measurement of the Brillouin spectrum along a spiral waveguide in a photonic integrated circuit. This approach gives access to local opto-acoustic properties of the waveguides, including the Brillouin frequency shift and linewidth, essential information for the further development of high quality photonic-phononic waveguides for SBS applications.

Background and objectiveCognitive impairments have been reported in patients with hyperprolactinemia; however, there is a lack of knowledge of brain structure alterations relevant to hyperprolactinemia in prolactinomas. Thus, we aimed to identify changes in brain structure in prolactinomas and to determine whether these changes are related to cognitive performance and clinical characteristics.MethodsParticipants were 32 female patients with prolactinomas and 26 healthy controls (HC) matched for age, sex, education, and handedness. All participants underwent magnetic resonance imaging brain scans, neuropsychological assessments, and clinical evaluations. Voxel-based morphometry analysis was used to identify changes in gray matter volume (GMV). Partial correlation analysis and multiple linear regression were performed to determine the relationship between GMV, cognition, and clinical characteristics.ResultsCompared to HC, patients with prolactinomas demonstrated a decrease in GMV in the left hippocampus, left orbitofrontal cortex, right middle frontal cortex (MFC), and right inferior frontal cortex (IFC). In addition, patients performed worse than controls on tests for verbal memory and executive function, and this was significantly related to the GMV of the left hippocampus and right MFC, respectively. Moreover, in the patients, we found a negative relationship between serum prolactin levels and the GMV of the left hippocampus and right IFC, whereas a positive relationship was found between the GMV of the left hippocampus and serum levels of estradiol and luteinizing hormone.ConclusionIn patients with prolactinomas, specific brain structure abnormalities have been identified and are associated with cognitive impairments and dysfunctional hormones. This study enhances our understanding of brain structure changes that may occur with prolactinomas and provides novel and fundamental evidence for previous behavioral findings relevant to hyperprolactinemia.