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Based on the ultrafast and extremely strong interaction between laser pulses and materials, ultrafast laser irradiation can break the solid solubility constraints and enable hyperdoping of impurities. This process overcomes the bandgap constraints of crystalline silicon, resulting in heightened absorption across a broad spectral range spanning from ultraviolet to infrared wavelengths, therefore commonly referred to as black silicon (b‐Si). The b‐Si demonstrates significant changes in optoelectronic properties, making it highly promising for applications in silicon photonics. Specifically, b‐Si photodetectors exhibit distinct advantages in terms of high photoelectric gain at low voltage, ultrabroadband spectral responsivity, large dynamic range, and suitability for operation over a wide temperature range. These properties address the limitations of traditional silicon photodetectors, showcasing great potential for applications in optoelectronic integration, artificial intelligence, information technology, energy devices, and beyond. This review focuses on b‐Si achieved through ultrafast laser processing, with a special emphasis on its applications in photodetectors. The mechanism of ultrafast laser irradiation and the properties of hyperdoped silicon are discussed. Then, the research progresses and state‐of‐the‐art b‐Si photodetectors are introduced, as well as working mechanism and potential application expansion. Finally, the development prospects of b‐Si photodetectors based on ultrafast laser hyperdoping are predicted. [ABSTRACT FROM AUTHOR]

The development of efficient and selective organic synthetic approaches for complex molecules has garnered significant attention due to the need for precise control over molecular structures and functions. Rotaxanes, a type of mechanically interlocked molecules (MIMs), have shown promising applications in various fields including sensing, catalysis, and material science. However, the highly selective synthesis of oligo[n]rotaxanes (mostly n≥3) through controlling host‐guest complexation and supramolecular threading assembly process still remains an ongoing challenge. In particular, the utilization of two‐dimensional (2D) macrocycles with structural shape‐persistency for the synthesis of oligo[n]rotaxanes is rare. In this concept, research on cooperatively threaded host‐guest complexation with hydrogen‐bonded (H‐bonded) aramide macrocycles and selective synthetic protocols of oligo[n]rotaxanes has been summarized. The high efficiency and selectivity in synthesis are ascribed to the synergistic interplay of multiple non‐covalent bonding interactions such as hydrogen bonding and intermolecular π–π stacking of macrocycles within the unique supramolecular structure of threaded host‐guest complexes. This review focuses on the latest progress in the concepts, synthesis, and properties of H‐bonded aramide macrocycle‐based oligorotaxanes, and presents an in‐depth outlook on challenges in this emerging field. [ABSTRACT FROM AUTHOR]

Recent advances in artificial intelligence technology and perception components have promoted the rapid development of autonomous vehicles. However, as safety‐critical software, autonomous driving systems often make wrong judgments, seriously threatening human and property safety. LiDAR is one of the most critical sensors in autonomous vehicles, capable of accurately perceiving the three‐dimensional information of the environment. Nevertheless, the high cost of manually collecting and labeling point cloud data leads to a dearth of testing methods for LiDAR‐based perception modules. To bridge the critical gap, we introduce MetaLiDAR, a novel automated metamorphic testing methodology for LiDAR‐based autonomous driving systems. First, we propose three object‐level metamorphic relations for the domain characteristics of autonomous driving systems. Next, we design three transformation modules so that MetaLiDAR can generate natural‐looking follow‐up point clouds. Finally, we define corresponding evaluation metrics based on metamorphic relations. MetaLiDAR automatically determines whether source and follow‐up test cases meet the metamorphic relations based on the evaluation metrics. Our empirical research on five state‐of‐the‐art LiDAR‐based object detection models shows that MetaLiDAR can not only generate natural‐looking test point clouds to detect 181,547 inconsistent behaviors of different models but also significantly enhance the robustness of models by retraining with synthetic point clouds. [ABSTRACT FROM AUTHOR]

A commutation torque ripple suppression strategy for the brushless DC motor (BLDCM) with commutation time is proposed. First, a torque model considering back electromotive force (back‐EMF) variation is presented, and the cause of commutation torque ripple is analysed. The results show that the commutation torque ripple of BLDCM is inevitable even if the non‐commutation current remains steady. On this basis, the influence and quantitative relationships of non‐commutation current and commutation time on commutation torque ripple are studied. Furthermore, two impact factors are proposed to comprehensively consider their effects on commutation torque ripple. The three‐phase windings are modulated in the commutation process at individual duty cycles. The comprehensive optimisation index of commutation torque ripple for different working conditions is obtained by calculating the relative relationship of the impact factors. The optimisation index determines the proper modulation duty cycles. Therefore, the motor parameters and working conditions do not limit the strategy. Finally, the experimental results verify the correctness of the theoretical analysis and the feasibility of the proposed strategy. The proposed strategy can reduce the commutation torque ripple by 16.28% and 21.80% and shorten the commutation time by 50.00% and 36.67% at low speed and high speed, respectively, compared with the conventional strategy. [ABSTRACT FROM AUTHOR]

Silicon‐based photodetectors show attractive prospects due to their convenient preparation, high detectivity, and complementary metal–oxide–semiconductor compatibility. However, they are currently limited by low responsivity and sharp decay at sub‐bandgap wavelength. Although the aforementioned limitation can be partly solved by femtosecond laser processing, the surface defects and carrier activation rates result in a large dark current and narrow spectral response, which are unsatisfactory. Herein, rapid thermal annealing and hydrogenated surface passivation are introduced to elevate the broad‐bandgap responsivity and signal to noise ratio and to suppress the dark current. At optimal conditions, a sub‐bandgap responsivity of 0.80 A W−1 for 1550 nm at 20 V at room temperature is obtained, comparable with commercial germanium photodiodes and much higher than previously reported silicon photodiodes. Moreover, the prepared photodetector responded to spectral range from 400 to 1600 nm, with responsivity reaching 1097.60 A W−1 for 1080 nm at 20 V, which is the highest in reported silicon photodetectors. Simultaneously, the device shows competitive detectivity (1.22 × 1014 Jones at −5 V) due to the post‐processing procedures and suppressed dark current (7.8 μA at −5 V). The results show great prospects for black silicon in infrared light detection, night vision imaging, and fiber‐optic communication. [ABSTRACT FROM AUTHOR]

The generation of multiple‐path test cases can greatly enhance the efficiency of path‐wise testing. Various methods adopting meta‐heuristic algorithm to generate multiple‐path test cases have been proposed, but existing methods focus on improving the meta‐heuristic algorithm to get better test case generation efficiency, and test cases covering each path needs to be generated by meta‐heuristic algorithm searching. To improve efficiency, a test case generation method for multiple‐path coverage is proposed in this study, which combines a particle swarm optimisation (PSO) algorithm with metamorphic relations (MRs). The method first generates a test case using the PSO algorithm, and then generates new test cases by repeatedly using MRs between test cases. This method reduces evolving numbers of PSO algorithm. The experimental results show that the proposed method can significantly enhance the efficiency in terms of fitness evaluations and time consumption. [ABSTRACT FROM AUTHOR]

This study proposes a novel inter‐turn fault diagnosis method for a permanent magnet synchronous machine. Search coils are set on every stator tooth to measure the tooth fluxes. The high‐order harmonics produced by the inverter are adopted to diagnose the inter‐turn fault existence and locate the fault tooth. The fault severity coefficient is proposed on the basis of theoretical analysis and can identify the fault severity. A comparative[AQ ID=Q1] analysis of a traditional method based on co‐simulation shows that the proposed method is sensitive and that the fault severity coefficient is accurate, intuitive and independent of the operating condition of the motor. An experimental platform is set up, and it validates the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Cartilage is a kind of special connective tissue which does not contain neither blood vessels nor lymphatics and nerves. Therefore, the damage in cartilage is difficult to be repaired spontaneously. Constructing tissue engineered cartilage provides a new technique for cartilage repairing. Mesenchymal stem cells (MSCs) possess a unique capability of self-renew and can differentiate into pre-chondrocytes which are frequently applied as seed cells in tissue engineering. However, in regenerated cartilage the chondrocytes derived from MSCs can hardly maintain homeostasis and preferentially present hypertrophic like phenotype. We investigated the effects of cyanidin, a natural organic compound, on chondrogenic and subsequent hypertrophic differentiation of MSCs in order to seek approaches to inhibit chondrocyte hypertrophy. We evaluated the effects of cyanidin on expression of chondrogenic and hypertrophic marker genes through RT-PCR, Western blot, alcian blue staining, and immunocytochemistry. The results showed that both chondrogenic related genes Sox9, Col2a1, and hypertrophic marker genes Runx2, Col10a1 were inhibited by cyanidin. In addition, we found that cyanidin promoted Nrf2 and p62 expression and suppressed LC3B expression during chondrogenic stage of MSCs. Meanwhile phosphorylation of IκBα and autophagosome related protein LC3B were inactivated by cyanidin during chondrocyte hypertrophic stage. Furthermore, rapamycin, an autophagy activator, abrogated the inhibitory effect of cyanidin on chondrogenic, and hypertrophic differentiation of MSCs. In conclusion, one potential mechanism of cyanidin, by which the chondrogenic and hypertrophic differentiation of MSCs were inhibited, was due to decreased autophagy activity. Our results indicated that cyanidin was a potential therapeutic agent for keeping mature chondrocyte functions. [ABSTRACT FROM AUTHOR]

Aims To assess the impact of a set of comprehensive tobacco control policies implemented in Taiwan in 2009, including extensive smoke-free policy, advertisement ban, pictorial warning and price increase, on adolescent smoking prevalence. Design Five waves of cross-sectional surveys. Setting Taiwan, 2004-11. Participants Nationally representative sample of junior high schools aged 13-15 years, in a biennial survey, total sample size 101 100. Measures Core questionnaire of the Global Youth Tobacco Survey, including ever smoking, 30-day smoking and number of cigarettes smoked. The magnitude of prevalence change before and after the 2009 policy implementation was quantified by adjusted odds ratios estimated by piecewise logistic regression models. Findings The 30-day smoking prevalence demonstrated an upward trend [odds ratio ( OR) = 1.06, 95% confidence interval ( CI) = 1.02-1.10] between 2004 and 2008. Significant decline in 30-day smoking prevalence after the 2009 law implementation was observed ( OR = 0.84, 95% CI = 0.71-0.99). Those living in non-city areas demonstrated a greater magnitude of change. In addition to changes in prevalence, we observed some delay in the age starting smoking, reduction in smokers who smoke fewer than one cigarette per day, and decrease in smokers who did not buy cigarettes. The decline in smoking prevalence was contributed primarily by the reduction in experimenters. Conclusion The comprehensive tobacco control programme introduced in Taiwan in 2009 was associated with a reduction in adolescent smoking, particularly among those in earlier stages of smoking and those who resided in non-city areas. [ABSTRACT FROM AUTHOR]

BackgroundThe occurrence of asthma may be associated with dietary factors. ObjectiveTo examine the association between nutrient intake and physician-diagnosed asthma and allergic rhinitis. MethodsA stratified, multiple-staged sampling design was used to select study areas, in which household interviews were carried out to gather information on health status and 24-h food recall. Data from 1166 adolescents, 13–17 years of age, were analysed. ResultsIn univariate analysis, total calorie and energy-adjusted fat intake were associated with the prevalence of asthma, whereas vitamin A and vitamin C intake showed negative association with asthma. Multivariate logistic regression was used to adjust for sex and levels of urbanization; intake of saturated fats was associated with increased risk (OR = 2.02 for an increase of one SD, 95%CI 1.40–2.90), while monounsaturated fats were inversely related to asthma (OR = 0.65 for an increase of one SD, 95%CI 0.43–0.99). Vitamin C intake in the lowest quartile was associated with elevated risk for asthma with marginal significance (OR = 1.81, 95%CI 0.88–3.71, P = 0.10). None of the nutritional factors was associated with allergic rhinitis. ConclusionResults from this cross-sectional survey suggest that saturated and monounsaturated fats may have different effects on airway inflammation. [ABSTRACT FROM AUTHOR]

Preclinical studies of nanoparticles for pulmonary therapeutics are often performed on 2D cell cultures or in vitro models that do not include a mucus barrier. However, the mucus layer lining the lungs is an essential barrier for drugs to permeate in order to exert a therapeutic effect. Herein, the role of surface coating of lanthanide‐doped upconverting nanoparticles (UCNPs) and their interaction with the mucus barrier are explored using a patient‐derived 3D cell culture model. The upconverted emissions from the UCNPs are used to track them throughout the 3D model and study their localization as a function of administration time and mucus thickness. Positively charged, ligand‐free, and negatively charged, supported lipid bilayer‐coated UCNPs are evaluated. A substantial difference in the residence time in mucus and mucociliary clearance of each type of UCNP is observed in a realistic and relevant model. As such, these results underscore the need for preclinical investigations in tissue models, especially with respect to the surface properties of the nanoparticles under study. [ABSTRACT FROM AUTHOR]

Although numerous studies on the impacts of climate change on biodiversity have been published, only a handful are focused on the intraspecific level or consider population‐level models (separate models per population). We endeavored to fill this knowledge gap relative to the Qinghai‐Tibetan plateau (QTP) by combining species distribution modeling (SDMs) with population genetics (i.e., population‐level models) and phylogenetic methods (i.e., phylogenetic tree reconstruction and phylogenetic diversity analyses). We applied our models to 11 endemic and widely distributed herpetofauna species inhabiting high elevations in the QTP. We aimed to determine the influence of environmental heterogeneity on species' responses to climate change, the magnitude of climate‐change impacts on intraspecific diversity, and the relationship between species range loss and intraspecific diversity losses under 2 shared socioeconomic pathways (SSP245 and SSP585) and 3 future periods (2050s, 2070s, and 2090s). The effects of global climatic change were more pronounced at the intraspecific level (22% of haplotypes lost and 36% of populations lost) than the morphospecies level in the SSP585 climate change scenario. Maintenance of genetic diversity was in general determined by a combination of factors including range changes, species genetic structure, and the part of the range predicted to be lost. This is owing to the fact that the loss and survival of populations were observed in species irrespective of the predicted range changes (contraction or expansion). In the southeast (mountainous regions), climate change had less of an effect on range size (>100% in 3 species) than in central and northern QTP plateau regions (range size <100% in all species). This may be attributed to environmental heterogeneity, which provided pockets of suitable climate in the southeast, whereas ecosystems in the north and central regions were homogeneous. Generally, our results imply that mountainous regions with high environmental heterogeneity and high genetic diversity may buffer the adverse impacts of climate change on species distribution and intraspecific diversity. Therefore, genetic structure and characteristics of the ecosystem may be crucial for conservation under climate change. [ABSTRACT FROM AUTHOR]

Introduction: End‐stage renal disease is a serious public health issue. The objective of this retrospective cohort study was to assess the association between hemodialysis and cognitive impairment, while controlling for age, sex, residence, and comorbidities. Methods: This study assesses the risk of cognitive impairment among a nationwide cohort of new hemodialysis patients derived from the NHIRD. Results: A total of 4330 patients were assigned to the dialysis group and 17 320 patients were assigned to the control group. A total of 2103 of the patients developed cognitive impairment within 2 years after the date of dialysis initiation. Patients who developed cognitive impairment were older (69.85 ± 11.56) than their counterparts who did not develop cognitive impairment (58.58 ± 14.77; P <.001). The log‐rank test of Kaplan‐Meier analysis revealed a higher risk of cognitive impairment in the hemodialysis group than in the non‐hemodialysis group (P <.001). The interval between dialysis initiation and the onset of cognitive impairment was 98.66 ± 46.39 months among non‐dialysis subjects and 53.45 ± 41.90 months among dialysis subjects, and the between‐group difference was significant (P <.001). The Cox Proportional Hazard Model revealed that after controlling for gender, age, residence, and comorbidities, hemodialysis was shown to have a significant impact on cognitive impairment (Hazard Ratio [HR]: 1.44; 95% confidence interval [CI]: 1.29‐1.60). Furthermore, the risk of developing cognitive impairment increased with age (HR: 1.07; 95% CI: 1.06‐1.08). Discussion Hemodialysis was associated with cognitive impairment. There was a significant association between age and cognitive impairment, regardless of the comorbidities prior to hemodialysis. There was no evidence of an association between comorbidities and cognitive impairment after beginning hemodialysis. [ABSTRACT FROM AUTHOR]

Aims To determine the induction effect of rifampicin on the activity of 4′-hydroxylase in poor metabolizers (PMs) with m[sub 1] mutation of S-mephenytoin 4′-hydroxylation and the relationship of the effect with gene dose. Methods Seven extensive metabolizers (EMs) of S-mephenytoin 4′-hydroxylation and five PMs with m[sub 1] mutation were chosen to take rifampicin 300 mg day[sup -1] orally for 22 days. Prior to and after rifampicin treatment, each subject was given racemic mephenytoin 100 mg. The 4′-hydroxymephenytoin (4′-OH-MP) excreted in the 0–24 h urine and mephenytoin S/R ratio in the 0–8 h urine were determined by h.p.l.c. and GC, respectively. Results In all EMs, the excretion of 4′-OH-MP in the 0–24 h urine was increased by 146.4±17.9%, 0–8 h urinary mephenytoin S/R ratio was decreased by 77.3±8.8%, the percentage increase in the 0–24 h excretion of 4′-OH-MP in those CYP2C19 homozygous (wt/wt) was greater than that in those heterozygous (wt/m[sub 1] and wt/m[sub 2] ) (203.9±42.5% vs 69.6±4.1%). 0–8 h urinary mephenytoin S/R ratio of those PMs with m[sub 1] mutation was decreased by 9.6%, the amount of 4′-OH-MP excreted in the 0–24 h urine was increased by 80.1±48.0%. Conclusions The activity of 4′-hydroxylase of PMs with m[sub 1] mutation of S-mephenytoin 4′-hydroxylation can be induced by rifampicin and the inducing effect of rifampicin on 4′-hydroxylase is gene dependent. [ABSTRACT FROM AUTHOR]

The composition and structure of the Yarlung Zangbo Suture Zone (YZSZ) provide important constraints on long‐standing disputes about the evolution of the Neo‐Tethys Ocean and continental collision. The Permian tectonic blocks (mainly composed of limestones and volcanic rocks) are widely distributed in the YZSZ. There are still different understandings about the origin of these blocks and their relationship with the evolution of the Neo‐Tethys Ocean. Here, we report the first reliable palaeomagnetic results of the Permian tectonic blocks in the Gyanyima and Mayum areas, the western segment of the YZSZ. Fossil records and our new zircon U–Pb results provide 254–252 Ma and 249 ± 2 Ma age constraints for the strata in the Gyanyima and Mayum sections, respectively. A total of 109 specimens were subjected to stepwise thermal demagnetizations. Among them, 83 specimens yielded interpretable results. After removing a recent geomagnetic field direction at low to intermediate temperature ranges, characteristic remanent magnetization (ChRM) directions can be isolated from the upper Permian–lower Triassic Gyanyima Formation (Fm). Unblocking temperature spectra of the ChRM indicate magnetite and haematite as the main carriers in the basalt and limestone/andesitic‐basalt samples, respectively. The ChRM passed the fold tests and a reversal test at 95% confidence level, indicating that it is most likely a primary remanence. The tilt‐corrected mean direction for 14 sites is D = 18.0°, I = −14.4°, k = 20.5, and α95 = 9.0°, which corresponds to a palaeolatitude of 7.3°S and a palaeopole at 48.3°N, 233.3°E with A95 = 8.1°. Combining the rock assemblage, palaeomagnetic, palaeontological, and geochronologic data, we conclude that these blocks were most likely seamounts formed in the low‐latitude area of the Neo‐Tethys Ocean. The palaeolatitude and origin of these blocks indicate that the evolution of the Neo‐Tethys Ocean was a complex process interspersed with the development of a series of seamounts and microblocks. [ABSTRACT FROM AUTHOR]

Use of abiotic chemical systems for understanding higher order superstructures is challenging. Here we report a ring‐in‐ring(s) system comprising a hydrogen‐bonded macrocycle and cyclobis(paraquat‐o‐phenylene) tetracation (o‐Box) or cyclobis(paraquat‐p‐phenylene) tetracation (CBPQT4+, p‐Box) that assembles to construct discrete higher order structures with adaptive conformation. As indicated by mass spectrometry, computational modeling, NMR spectroscopy, and single‐crystal X‐ray diffraction analysis, this ring‐in‐ring(s) system features the box‐directed aggregation of multiple macrocycles, leading to generation of several stable species such as H4G (1 a/o‐Box) and H5G (1 a/o‐Box). Remarkably, a dimeric shish‐kebab‐like ring‐in‐rings superstructure H7G2 (1 a/o‐Box) or H8G2 (1 a/p‐Box) is formed from the coaxial stacking of two ring‐in‐rings units. The formation of such unique dimeric superstructures is attributed to the large π‐surface of this 2D planar macrocycle and the conformational variation of both host and guest. [ABSTRACT FROM AUTHOR]

Use of abiotic chemical systems for understanding higher order superstructures is challenging. Here we report a ring‐in‐ring(s) system comprising a hydrogen‐bonded macrocycle and cyclobis(paraquat‐o‐phenylene) tetracation (o‐Box) or cyclobis(paraquat‐p‐phenylene) tetracation (CBPQT4+, p‐Box) that assembles to construct discrete higher order structures with adaptive conformation. As indicated by mass spectrometry, computational modeling, NMR spectroscopy, and single‐crystal X‐ray diffraction analysis, this ring‐in‐ring(s) system features the box‐directed aggregation of multiple macrocycles, leading to generation of several stable species such as H4G (1 a/o‐Box) and H5G (1 a/o‐Box). Remarkably, a dimeric shish‐kebab‐like ring‐in‐rings superstructure H7G2 (1 a/o‐Box) or H8G2 (1 a/p‐Box) is formed from the coaxial stacking of two ring‐in‐rings units. The formation of such unique dimeric superstructures is attributed to the large π‐surface of this 2D planar macrocycle and the conformational variation of both host and guest. [ABSTRACT FROM AUTHOR]

Understanding how and why species evolve requires knowledge on intraspecific divergence. In this study, we examined intraspecific divergence in the endangered hot‐spring snake (Thermophis baileyi), an endemic species on the Qinghai‐Tibet Plateau (QTP). Whole‐genome resequencing of 58 sampled individuals from 15 populations was performed to identify the drivers of intraspecific divergence and explore the potential roles of genes under selection. Our analyses resolved three groups, with major intergroup admixture occurring in regions of group contact. Divergence probably occurred during the Pleistocene as a result of glacial climatic oscillations, Yadong‐Gulu rift, and geothermal fields differentiation, while complex gene flow between group pairs reflected a unique intraspecific divergence pattern on the QTP. Intergroup fixed loci involved selected genes functionally related to divergence and local adaptation, especially adaptation to hot spring microenvironments in different geothermal fields. Analysis of structural variants, genetic diversity, inbreeding, and genetic load indicated that the hot‐spring snake population has declined to a low level with decreased diversity, which is important for the conservation management of this endangered species. Our study demonstrated that the integration of demographic history, gene flow, genomic divergence genes, and other information is necessary to distinguish the evolutionary processes involved in speciation. [ABSTRACT FROM AUTHOR]

The PI3K‐AKT signaling pathway regulates cell survival, proliferation, and migration. An abnormal activation of PI3K plays an important role in cancer development. Here, we identify TRAF6 as a potent E3 ubiquitin ligase for the PI3K catalytic subunit PIK3CA (p110α). TRAF6 interacts with PIK3CA and promotes its nonproteolytic polyubiquitination under serum stimulation. TRAF6 ubiquitinates both individual and regulatory subunit‐bound PIK3CA but does not ubiquitinate the regulatory subunit of PI3K. The examination of TRAF6 mRNA expression revealed its upregulation in multiple human malignancies. We demonstrate that overexpression of TRAF6 greatly enhances PI3K activation, leading to an increase in AKT phosphorylation and cell growth. We conclude that TRAF6 is a novel PIK3CA regulator whose deregulated overexpression represents a mechanism for PI3K overactivation in tumors. [ABSTRACT FROM AUTHOR]

The anode‐cathode interplay is an important but rarely considered factor that initiates the degradation of aqueous zinc ion batteries (AZIBs). Herein, to address the limited cyclability issue of V‐based AZIBs, Al2(SO4)3 is proposed as decent electrolyte additive to manipulate OH−‐mediated cross‐communication between Zn anode and NaV3O8 ⋅ 1.5H2O (NVO) cathode. The hydrolysis of Al3+ creates a pH≈0.9 strong acidic environment, which unexpectedly prolongs the anode lifespan from 200 to 1000 h. Such impressive improvement is assigned to the alleviation of interfacial OH− accumulation by Al3+ adsorption and solid electrolyte interphase formation. Accordingly, the strongly acidified electrolyte, associated with the sedated crossover of anodic OH− toward NVO, remarkably mitigate its undesired dissolution and phase transition. The interrupted OH−‐mediated communication between the two electrodes endows Zn||NVO batteries with superb cycling stability, at both low and high scan rates. [ABSTRACT FROM AUTHOR]

The anode‐cathode interplay is an important but rarely considered factor that initiates the degradation of aqueous zinc ion batteries (AZIBs). Herein, to address the limited cyclability issue of V‐based AZIBs, Al2(SO4)3 is proposed as decent electrolyte additive to manipulate OH−‐mediated cross‐communication between Zn anode and NaV3O8 ⋅ 1.5H2O (NVO) cathode. The hydrolysis of Al3+ creates a pH≈0.9 strong acidic environment, which unexpectedly prolongs the anode lifespan from 200 to 1000 h. Such impressive improvement is assigned to the alleviation of interfacial OH− accumulation by Al3+ adsorption and solid electrolyte interphase formation. Accordingly, the strongly acidified electrolyte, associated with the sedated crossover of anodic OH− toward NVO, remarkably mitigate its undesired dissolution and phase transition. The interrupted OH−‐mediated communication between the two electrodes endows Zn||NVO batteries with superb cycling stability, at both low and high scan rates. [ABSTRACT FROM AUTHOR]

Naturalized plants play pivotal roles in local plant biodiversity and ecological functions; however, the drivers of naturalization remain poorly understood at a fine scale. Thus, understanding the processes of the development and dominance of alien plants in local natural habitats is of paramount importance. In the present study, we report for the first time the naturalization of Cydonia oblonga in China based on community structure and population dynamics at a fine scale. We conducted a comprehensive survey of the species through field community investigations, interviews, and a literature review. Cydonia oblonga is an ancient fruit tree with a long introduction history of over 4500 years worldwide and a cultivation history of over 2500 years in China. We analyzed C. oblonga community structure using the spatiotemporal substitution method and quantitatively analyzed population dynamics using a static life table, survivorship curve, and time series model to explore the naturalization processes. The following results were obtained. (i) The community comprised 31 coexisting vascular plant species (16 woody and 15 herbaceous species) belonging to 28 genera in 20 families. Rosaceae and Asteraceae were the two most dominant families. (ii) All individuals in the shrub layer as well as the C. oblonga population exhibited a roughly inverted J‐shaped basal diameter distribution. A complete age structure was noted, and the survival curve was classified as Deevey type II. According to time series analysis, the population is estimated to increase in the future, specifically of medium and large individuals. (iii) Religious exchange, potent resource competitiveness, and similarity with the native habitat may be the major drivers of the introduction and successful naturalization of C. oblonga. These results suggest that alien species closely related to native ones are more likely to invade, naturalize, and dominate communities in local habitats. [ABSTRACT FROM AUTHOR]

Summary: The insect pathogenic fungus, Metarhizium anisopliae is a commercialized microbial agent used in biological control efforts targeting a diverse range of agricultural and other insect pests. The second step in the synthesis of a group of M. anisopliae α‐pyrone diterpenoids (termed subglutinols) involves the activity of a prenyltransferase family geranylgeranyl diphosphate synthase (product of the subD/MaGGPPS5 gene). Here, we show that targeted gene disruption of MaGGPPS5 results in earlier conidial germination and faster greater vegetative growth compared to the wild type (WT) parent and complemented strains. In addition, insect bioassays revealed that the ΔMaGGPPS5 mutant strain displayed significantly increased virulence, with a ~50% decrease in the mean lethal time (LT50, from 6 to 3 days) to kill (50% of) target insects, and an ~15–40‐fold decrease in the mean lethal dose (LC50). Metabolite profiling indicated increased accumulation in the ΔMaGGPPS5 mutant of select subglutinols (A, B and C) and destruxins (A, A2, B and B2), the latter a set of fungal secondary metabolites that act as insect toxins, with a concomitant loss of production of subglutinol 'analogue 45'. These data suggest that the increased virulence phenotype seen for the ΔMaGGPPS5 strain can, at least in part, be attributed to a combination of faster growth and increased insect toxin production, linking the production of two different secondary metabolite pathways, and represent a novel approach for the screening of isolates with enhanced virulence via modulation of terpenoid secondary metabolite biosynthesis. [ABSTRACT FROM AUTHOR]

Dispersion occurs naturally in many wave systems. So far, a variety of techniques have been proposed and demonstrated to compensate the second‐order (group‐velocity) dispersion, such as dispersion management and nonlinear soliton formation, yet it is commonly believed that the first‐order dispersion (FOD) is less amenable and cannot be eliminated. In this work, it is shown that a phase‐invariant propagation of THz pulses, namely the "frozen‐phase" propagation, can be realized by a complete cancellation of the FOD, achieved by implementing a synchronized THz moving source with a locked initial phase. The dynamic generation and propagation process of the THz pulses is examined directly by a time‐resolved imaging system. To the best of authors' knowledge, this represents the first demonstration of the "frozen‐phase" propagation of a light pulse in dispersive optical systems. [ABSTRACT FROM AUTHOR]

Influenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is high. It is important to develop broad‐spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti‐influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, that is, irreversibly inhibit viral infectivity. Here, a new class of broad‐spectrum anti‐influenza macromolecules is described that meets these criteria and display exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated either in 6'sialyl‐N‐acetyllactosamine (6'SLN) or in 3'SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, it is shown that, in mice, one of the compounds provides therapeutic efficacy when administered 24 h post‐infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir. [ABSTRACT FROM AUTHOR]

Aims The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. Methods A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5–7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. Results Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0,∞), P < 0.001), 113% increase in terminal elimination half-life (t½) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean ± (s.d) norfluoxetine AUC(0,192 h) was significantly lower in PMs than that in EMs (1343 ± 277 vs 2935 ± 311, P < 0.001). Mean fluoxetine Cmax and AUC(0,∞) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 ± 3.9 vs 36.7 ± 8.9, P < 0.001; 732 ± 42 vs 2152 ± 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 ± 3.4 vs 36.0 ± 8.7, P < 0.01; 54.7 ± 3.4 vs 20.6 ± 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0,192 h) in PMs was significantly lower than that in wild type homozygotes (1343 ± 277 vs 3163 ± 121, P < 0.05) and that in heterozygotes (1343 ± 277 vs 2706 ± 273, P < 0.001), respectively. Conclusions The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N-demethylation among Chinese healthy subjects. [ABSTRACT FROM AUTHOR]

Monilinia fructicola is the most widely distributed species among the Monilinia genus in the world, and causes blossom blight, twig canker, and fruit rot on Rosaceae fruits. To date, studies on genomics and pathogenicity are limited in M. fructicola. In this study, we identified a redox‐related gene, MfOfd1, which was significantly up‐regulated at 1 hr after inoculation of M. fructicola on peach fruits. We used the clustered regulatory inter‐spaced short palindromic repeats (CRISPR)/Cas9 system combined with homologous recombination to determine the function of the MfOfd1 gene. The results showed that the sporulation of knockdown transformants was reduced by 53% to 83%. The knockdown transformants showed increased sensitivity to H2O2 and decreased virulence on peach fruits compared to the wild‐type isolate Bmpc7. It was found that H2O2 could stimulate the expression of MfOfd1 in the wild‐type isolate. The transformants were also more sensitive to exogenous osmotic stress, such as glycerol, d‐sorbitol, and NaCl, and to dicarboximide fungicides (iprodione and dimethachlon). These results indicate that the MfOfd1 gene plays an important role in M. fructicola in sporulation, oxidative response, osmotic stress tolerance, and virulence. [ABSTRACT FROM AUTHOR]

Background and Purpose: Effective anti-respiratory syncytial virus (RSV) agents are still not available for clinical use. Current major targets are virus surface proteins, such as a fusion protein involved in viral entry, but agents effective after RSV infection is established are required. Here we have investigated the effects of late therapeutic intervention with a novel inhaled RSV polymerase inhibitor, PC786, on RSV infection in human airway epithelium.Experimental Approach: Air liquid interface-cultured bronchial or small airway epithelium was infected with RSVA2. PC786 was applied apically or basolaterally once daily following peak virus load on Day 3 post inoculation. Apical wash was collected daily for determination of viral burden by PCR and plaque assay (primary endpoints) and biomarker analyses. The effects were compared with those of ALS-8112, an anti-RSV nucleoside analogue, and GS-5806, a fusion-protein inhibitor, which were treated basolaterally.Key Results: Late intervention with GS-5806 did not show significant anti-viral effects, but PC786 produced potent, concentration-dependent inhibition of viral replication with viral load falling below detectable limits 3 days after treatment commenced in airway epithelium. These effects were superior to those of ALS-8112. PC786 showed inhibitory activities against RSV-induced increases of CCL5, IL-6, double-strand DNA and mucin. The effects of PC786 were also confirmed in small airway epithelium.Conclusion and Implications: Late therapeutic intervention with the RSV polymerase inhibitor, PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786 demonstrates the potential to be an effective therapeutic agent to treat active RSV infection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: RNA interference (RNAi) refers to the phenomenon of sequence-specific degradation of homologous mRNA induced by double-stranded RNA. It has been successfully utilized to down-regulate endogenous gene expression or suppress the replication of various pathogens in mammalian cells. In this study, the effect of vector-based small interfering RNA (siRNA) promoted by pSilencer2.0-U6 inhibit hepatitis B virus (HBV) replication in cell culture was evaluated. METHODS: Three fragments of short nucleic acids, respectively, targeting on S, X and C region of HBV genome were inserted into pSilencer vectors after they were annealed with their partly antisense strands. The recombination plasmids were pS, pX and pC. These expression plasmids were transfected into HepG2-N10 cells, a cell line which stably expresses hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg) and adw2 subtype Dane particles. The effect of RNAi was evaluated from the changes of DNA, RNA and protein levels. Viral antigens were measured by ELISA. Viral mRNA was analyzed by RT-PCR. The covalent closed circular DNA and genome DNA of HBV secreted into the culture media were measured by quantitative real-time PCR. Analysis of variance was performed for the results. RESULTS: Vector-based RNA interference could potently reduce HBsAg (pS vs pN: 47%, pX vs pN: 30%, and pC vs pN: 25%, P < 0.001) and HBeAg (pX vs pN: 57% and pC vs pN: 66%, P < 0.001) expression in cell culture. Furthermore, RT-PCR analysis showed that viral mRNAs were effectively degraded, thus eliminating the messengers for protein expression as well as templates for reverse transcription (pS and pC vs pN, P < 0.001; pX vs pN, P = 0.003). Quantitative real-time PCR analysis of HBV DNA revealed that vector-based RNA interference can inhibit HBV replication efficiently (pS, pX and pC vs pN, P < 0.001). CONCLUSIONS: Our results indicate that RNAi can inhibit HBV gene expression and replication, and it might have the potential to revolutionize the treatment of HBV. [ABSTRACT FROM AUTHOR]

Introduction The effect of medical education is often hard to evaluate. We tried to assess whether a 2-hour, small-group discussion could alter student perspectives on truth telling. Currently, in Taiwan it is common practice to consult with the family of a terminally ill patient before telling the truth to the patient, which may be in conflict with patient autonomy. Methods The study was based on content analysis of self-reflective written texts after a 2-hour group discussion on a clinical case describing a truth-telling situation. The changes in decision patterns regarding the emphasis placed on patient autonomy versus family paternalism and the connection to related moral reasoning were subjected to focus analysis. Results The students' initial attitudes regarding the subject of truth telling were categorised into 4 patterns, namely, patient-centred ( n = 46), family-centred ( n = 20), simultaneous informing ( n = 1), and situational informing ( n = 5) modes. The discussion stimulated perspective changes in many of the students and their attitudes were then regrouped as patient-comprehensive ( n = 35), family-centred ( n = 1), and family-comprehensive ( n = 36) modes. It was found that variations on ‘common sense’ and moral reasoning existed prior to the class and the students initially tended to overlook the complexity of truth telling in terminal cancer. Through the discussion and reflective learning, they were enabled to acknowledge the vulnerability of both the patient and his or her family, and to make decisions based on more comprehensive considerations. Conclusion Group discussion seemed to be able to enhance ethical consideration. Further research is required to determine whether the benefits of this approach can be translated into behavioural changes in practice. [ABSTRACT FROM AUTHOR]

Aims To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity. Methods Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1′-hydroxymidazolam:midazolam (1′-OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1′-OH-MDZ and MDZ in plasma were measured by HPLC Results A 13-fold variation of CYP3A activity (log1′-OH-MDZ:MDZ: range -0.949–0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov–Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05). Conclusions A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle. [ABSTRACT FROM AUTHOR]

Aims The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. Methods The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. Results The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent K[sub m] values for the high-and low-affinity components were 1.9 and 88 μm and V [sub max] values were 33 and 554 pmol min[sup -1] mg[sup -1] protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. Conclusions The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway. [ABSTRACT FROM AUTHOR]