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【Objective】Aiming at the problems of low spectral efficiency and limited system throughput in Optical Quadrature Spatial Modulation (OQSM), a Signed Optical Quadrature Spatial Modulation (SOQSM) scheme is proposed in Free Space Optical Communication (FSOC) in this paper. In addition, in view of the fact that the channel used in the performance analysis of OQSM is not suitable for all turbulence, this paper also adopts the Málaga channel, which is suitable for all turbulence intensities to analyze the bit error performance of the system.【Methods】First, the scheme divides the input binary bit stream into five parts at the sending end. The first part is used for constellation symbol mapping, and the last four parts are used for laser mapping. Then, the constellation symbol mapping is used to transmit the real and imaginary parts of the constellation symbol and its inverse symbol. The laser mapping is divided into two parts, the in-phase phase and the quadrature phase, which are used to activate the laser sequence mapping. Finally, after transmitting through the channel, the signal received and processed at the receiving end.【Results】Compared with OQSM, SOQSM carries an additional2log2Nt bits of information in the space domain within a transmission period. The upper bound of the average bit error rate is then calculated in the symbol domain and the space domain respectively. Finally, the upper bound of the average bit error rate of the SOQSM scheme is obtained, and the method of calculating the upper bound of the average bit error rate has good convergence. This solution greatly improves the spectral efficiency and transmission rate of the system, and has good bit error rate performance.【Conclusion】The Monte Carlo simulation results show that compared with Optical Spatial Modulation (OSM) and OQSM, the bit error performance of the SOQSM scheme is better when the spectral efficiency is the same. The bit error rate can reach 10-6 when the signal-to-noise ratio is 16dB. When the modulation order is the same, the bit error performance of SOQSM is better, especially when the signal-to-noise ratio is high. It is also shown that the simulation and theory fit well. In the Málaga channel, the bit error rate performance of the weak turbulence is better. In addition, different turbulence intensities have little influence on the trend of the bit error rate performance of the SOQSM scheme. However, with the increase of the signal-to-noise ratio, the influence will gradually increase. Therefore, SOQSM has better bit error rate performance than OQSM and OSM.

Acquired resistance in Candida albicans brings about a serious challenge to the clinical application of azoles, so it is urgent to elucidate the mechanisms of azole resistance to improve the therapeutic efficiency. In the aim of searching for the potential targets mediating fluconazole resistance, we screened a mutant library of 48 transcription factor deletion Candida albicans strains. The screening results showed that hap2Δ/Δ mutants were significantly more susceptible to azoles, especially to miconazole (MCZ). Under MCZ treatment, the intracellular reactive oxygen species (ROS) were significantly higher in hap2Δ/Δ mutants compared to the control strain SN250. The addition of antioxidants reversed the MCZ-sensitive phenotype caused by the deletion of HAP2. Consistently, the expression of antioxidases responsible for scavenging ROS was shown to decrease in hap2Δ/Δ mutants, suggesting that the transcription factor Hap2p is involved in the regulation of oxidative stress responses in C. albicans. In addition, HAP2 deficiency also resulted in impaired mitochondrial function and affected cellular energy supply, which may be related to the iron deficiency regulated by HAP complex. HAP2 disruption also decreased efflux-mediated resistance of C. albicans, as demonstrated by a significant decrease in Cdr1p expression and a slight decrease in Mdr1p expression in hap2Δ/Δ strains under the action of MCZ. The above results indicate that the transcription factor Hap2p was required for the resistance of C. albicans to azoles, which could provide a new strategy to solve the clinical azoles resistance. [ABSTRACT FROM AUTHOR]

TB18 is a newly developed high-strength metastable β-titanium alloy, commonly used in aerospace structural materials, which demands high mechanical performance. By altering the alloy's microstructure, heat treatment can affect its mechanical characteristics. The alloy was solution treated for one to four hours at 870 °C in order to examine the impact of solution treatment duration. Using X-ray diffraction (XRD) and scanning electron microscopy (SEM), the effects of solution treatment time on the β-phase grain size and its effect on stress distribution during tensile testing were examined. The findings showed that stress concentration during the tensile process was successfully decreased by refining the β-phase grain size. Sample solutions treated for two hours at 870 °C were then aged at various temperatures (510 °C, 520 °C, 530 °C, and 540 °C) to examine the impact of aging temperature. While the mass proportion of the α-phase first climbed and subsequently declined, reaching its maximum at 530 °C, the size of the α-phase increased monotonically as the aging temperature increased. The varies of mass fraction is associated with how the aging temperature affects α-phase nucleation. Tensile studies on TB18 alloy aged at various temperatures showed that while the alloy's ductility reduced, its strength increased as the aging temperature rose. The Hall-Petch relationship explains this tendency. [ABSTRACT FROM AUTHOR]

More than 60 million children have been left behind in rural China by parents going to work in cities. Given the effects of child-parent separation (CPS) on development, this phenomenon has drawn considerable governmental and academic attention in recent years. Outlining developments with reference to relevant studies, this review characterizes the perspectives used to explore and understand this phenomenon in terms of three major paradigms: (1) the diagnostic approach, which takes for granted the assumption that CPS would be the only cause of negative effects observed among left-behind children (LBC), and has focused primarily on measuring psychological and behavioral disorders among these "problematic kids"; (2) the advanced diagnostic approach, which refines the previous approach by incorporating theories and techniques developed outside of China, elaborating on the early approach by bringing into consideration more factors and exploring the interactions between CPS and these factors, particularly social ones; (3) the sociologically oriented approach, which provides the research with a much broader framework in terms of how to orient the phenomenon of LBC, especially the transformation of China's social and economic systems during the last 30 years of urbanization, where the reproduction of labor has been based on a "splitting family structure," such that problems associated with the phenomenon of LBC cannot be solved without systematic social and economic changes. Based on these analyses, future directions for research on LBC in China are also discussed.

Toll-like receptor 7/8 (TLR-7/8) agonists serve as a promising class of pattern recognition receptors that effectively evoke the innate immune response, making them promising immunomodulatory agents for tumor immunotherapy. However, the uncontrollable administration of TLR-7/8 agonists frequently leads to the occurrence of severe immune-related adverse events (irAEs). Thus, it is imperative to strategically design tumor-microenvironment-associated biomarkers or exogenous stimuli responsive TLR-7/8 agonists in order to accurately evaluate and activate innate immune responses. No comprehensive elucidation has been documented thus far regarding TLR-7/8 immune agonists that are specifically engineered to enhance immune activation. In this feature article, we provide an overview of the advancements in TLR-7/8 agonists, aiming to enhance the comprehension of their mechanisms and promote the clinical progression through nanomedicine strategies. The current challenges and future directions of cancer immunotherapy are also discussed, with the hope that this work will inspire researchers to explore innovative applications for triggering immune responses through TLR-7/8 agonists. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The present study aimed to quantitatively investigate the potential drug–drug interaction (DDI) mechanism between meropenem (MEPM) and valproic acid (VPA).In the present study, we firstly developed a physiologically based pharmacokinetic (PBPK) model of MEPM and VPA. The verified PBPK model was then used to quantitatively investigate the potential DDI between MEPM and VPA. The effect of genetic polymorphisms of acylpeptide hydrolase (APEH) on DDI was also evaluated.In our simulation, the plasma concentration of hydrolysate of VPAG decreased to 63% when combined with MEPM. Total plasma concentration of VPA before carbapenem use was 53.61 mg/L, whereas it was 45.42 mg/L during carbapenem use. The inhibition of hydrolysis of VPAG by MEPM alone could not result in a rapid and substantial decrease in the plasma concentration of VPA. Parameter sensitivity analysis showed that the changes of absorption played an important role in the maximum plasma concentration (Cmax) of VPA, whereas area under the plasma concentration–time profile (AUC) was more susceptible to elimination changes. In addition, a decrease in APEH activity had little impact on the plasma pharmacokinetics of VPA.The DDI between MEPM and VPA might be a comprehensive result of multiple factors. On the basis of our simulation, interval medication of MEPM injection and VPA immediate release tablet at 4–6 h timed interval was recommended, or intravenous administration of VPA solution was preferred when combination regimen was necessary in a clinical setting. [ABSTRACT FROM AUTHOR]

Candida albicansis a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence,C. albicanscould either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay betweenCandida albicansand the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invadedC. albicansincluding the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. [ABSTRACT FROM AUTHOR]