Although ethanol treatment is widely used to activate oocytes, the underlying mechanisms are largely unclear. Roles of intracellular calcium stores and extracellular calcium in ethanol-induced activation (EIA) of oocytes remain to be verified, and whether calcium-sensing receptor (CaSR) is involved in EIA is unknown. This study showed that calcium-free ageing (CFA) in vitro significantly decreased intracellular stored calcium (sCa) and CaSR expression, and impaired EIA, spindle/chromosome morphology and developmental potential of mouse oocytes. Although EIA in oocytes with full sCa after ageing with calcium does not require calcium influx, calcium influx is essential for EIA of oocytes with reduced sCa after CFA. Furthermore, the extremely low EIA rate in oocytes with CFA-downregulated CaSR expression and the fact that inhibiting CaSR significantly decreased the EIA of oocytes with a full complement of CaSR suggest that CaSR played a significant role in the EIA of ageing oocytes. In conclusion, CFA impaired EIA and the developmental potential of mouse oocytes by decreasing sCa and downregulating CaSR expression. Because mouse oocytes routinely treated for activation (18 h post hCG) are equipped with a full sCa complement and CaSR, the present results suggest that, while calcium influx is not essential, CaSR is required for the EIA of oocytes.

There are few studies on the intelligent guidance of unmanned sailboats, which should coordinate pluralistic tasks at sea in the nature of its maneuvring intractability. To ensure the algorithmic practicability, this paper proposes a path-following and collision-avoidance guidance approach of unmanned sailboats with total formulaic description. The risk-detecting mechanism is fabricated by setting a circular detecting zone and using the time to the closest point of approach. Then, the risk of collision, the path deviation, the speed loss, and the course loss can be judged by constructing the cost functions and applying the distance to closest point of approach. The optimized heading angle is deemed as the one minimizing the aggregate cost functions, which is sought by applying and improving the beetle antennae search (BAS) algorithm. In the proposed modified BAS, the searching step is redesigned to enhance the searching efficiency. To ensure the convergence of the real heading angle to the reference, the backstepping-based control law is fabricated for the high-order sailboat model and in the linear form. The control parameters are offline optimized through the modified BAS. Compared with the adaptive control, this controller can guarantee more computation simplicity and the optimized control performance. Finally, simulation corroborates that the sailboat can successfully complete path following and collision avoidance while encountering multiple static and moving obstacles under the proposed schemes.

In this paper, the reflection of curved shock waves over a symmetry plane in planar supersonic flow is studied. This includes stable Mach reflection (MR) and the regular reflection (RR) to MR transition process. Curved shock theory (CST) is applied to derive the high-order parameters in front of and behind the shock wave. The method of curved shock characteristics is used to establish an analytical model to predict the wave configurations. The shock structures provided by the proposed model agree well with the numerical results. Flow structures, such as the height of the Mach stem and the shape of the shock wave and slip line, are studied by applying the analytical model. Isentropic waves generated from a curved wall are found to significantly influence the flow patterns. It appears that the compression waves obstruct the formation of the sonic throat and increase the Mach-stem height. The expansion waves have the opposite effect. The evolution mechanism of the Mach stem is found in conjunction with the RR-to-MR transition process. The CST is extended to a moving frame and used to model the transition. The time history of the moving triple point illustrates the effects of the incident shock angle and isentropic waves on the transition process.

High-speed water entry is a transient hydrodynamic process that is accompanied by strongly compressible flow, free surface splash, cavity evolution and other nonlinear hydrodynamic phenomena. To address these problems, a novel fluid–structure interaction (FSI) scheme based on the immersed boundary method is proposed which is suitable for strongly compressible multiphase flows. In this scheme, considering the multiphase interfaces at the immersed boundary, an improved immersed boundary method for effectively suppressing the non-physical force oscillation is proposed. Additionally, a quaternion-based six degrees of freedom motion system is used to describe rigid body motion, and the multiphase flow Eulerian finite element method is applied as the fluid solver. Using analytical solutions, experimental data and literature data, the accuracy and robustness of the FSI scheme are validated. Finally, the high-speed water entry of the slender body with different noses is investigated, and the hydrodynamic loads including the axial and normal drag forces and the bending moment are extensively discussed. The hydrodynamic load and motion trajectory are determined by the nose configuration. The tail slamming phenomenon is the primary focus, and it is revealed that its formation is primarily related to the pitch moment formed at the stage of crossing the free surface. Tail slamming also causes violent impact loads, especially bending moments, which may cause slender projectiles to break off. Finally, to combine the features of the flat and hemispherical noses, the water entry of the projectile with a truncated hemispherical nose is simulated and discussed.

Parametric interaction allows both forward and backward energy transfers among the three interacting waves. The back-conversion effect is usually detrimental when unidirectional energy transfer is desired. In this theoretical work, we manifest that the back-conversion effect underpins the direct generation of the picosecond pulse train without the need for a laser resonator. The research scenario is an optical parametric amplification (OPA) that consists of a second-order nonlinear medium, a quasi-continuous pump laser and a sinusoidal amplitude-modulated seed signal. The back-conversion of OPA can transfer the modulation peaks (valleys) of the incident signal into output valleys (peaks), which inherently induces spectral sidebands. The generation of each sideband is naturally accompanied with a phase shift of ±π. In the regime of full-back-conversion, the amount and amplitude of the sidebands reach the maximum simultaneously, and their phase constitutes an arithmetic sequence, leading to the production of a picosecond pulse train. The generated picosecond pulse train can have an ultrahigh repetition rate of 40 GHz or higher, which may facilitate ultrafast applications with ultrahigh speed.

Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

The northern Alxa region is located in the central segment of the southern Central Asian Orogenic Belt. Many controversies and deficiencies still exist regarding the magma source characteristics, petrogenesis and tectonic regimes during the late Palaeozoic – early Mesozoic period within this region. This study presents whole-rock compositions and zircon U–Pb and Lu–Hf isotopic data for three early Mesozoic I- and A-type granitic plutons occurring in the northern Alxa region. The Haerchaoenji and Chahanhada I-type granitoids yielded zircon 206Pb–238U ages of 245 ± 5 Ma and 245 ± 2 Ma, respectively. The variable positive zircon ϵHf(t) values between +1.8 and +11.8, with young TDM ages of 425–837 Ma, indicate that these I-type granitoids were mainly derived from juvenile crustal materials. The Wulantaolegai pluton has a zircon 206Pb–238U age of 237 ± 2 Ma and is classified as having high-K calc-alkaline A-type affinity. Furthermore, the positive zircon ϵHf(t) values of the Wulantaolegai granite range from +3.3 to +8.7 with young TDM ages of 545–778 Ma, suggesting the involvement of a juvenile crustal source as well. Furthermore, the major-element compositions of the Chahanhada and Wulantaolegai granites suggest the input of metasedimentary components. Geochemically, the Haerchaoenji and Chahanhada I-type granitoids show an arc affinity, while the Wulantaolegai granite exhibits a post-collisional affinity. However, with regional data, we suggest that the Haerchaoenji and Chahanhada I-type granitoids were also emplaced in a post-collisional setting, and the arc affinity was probably inherited from recycled subduction-related materials. These lines of evidence obtained in this study enable us to argue that the Palaeo-Asian Ocean in the central segment of the Central Asian Orogenic Belt closed before Middle Triassic time.

Interpretation bias (i.e. the selective negative interpretation of ambiguous stimuli) may contribute to the development and maintenance of health anxiety. However, the strength of the empirical evidence for this association remains a topic of debate. This study aimed to estimate the association between health anxiety and interpretation bias and to identify potential moderators of this association. Chinese-language databases (CNKI, VIP, and Wanfang), English-language databases (Web of Science, PubMed, PsycINFO, and Scopus), and German-language databases (Psyndex and PubPsych) were searched for relevant studies. There were 36 articles (39 studies) identified by this search (N = 8984), of which 32 articles (34 studies) were included in the meta-analysis (N = 8602). Results revealed a medium overall effect size (g = 0.67). Statistically equivalent effect sizes were observed for patients diagnosed with clinical health anxiety (g = 0.58) and subclinical health anxiety (g = 0.72). The effect sizes for threat stimuli that were health related (g = 0.68) and not health related (g = 0.63) did not differ significantly. The effect size for studies using an offline paradigm (g = 0.75) was significantly higher than that for studies using an online paradigm (g = 0.50). It is concluded that health anxiety is significantly and robustly associated with interpretation bias. These findings are of central importance for the advancement of models and treatment of health anxiety.

We present an experimental study of Rayleigh–Bénard convection using liquid metal alloy gallium-indium-tin as the working fluid with a Prandtl number of $Pr=0.029$. The flow state and the heat transport were measured in a Rayleigh number range of $1.2\times 10^{4} \le Ra \le 1.3\times 10^{7}$. The temperature fluctuation at the cell centre is used as a proxy for the flow state. It is found that, as $Ra$ increases from the lower end of the parameter range, the flow evolves from a convection state to an oscillation state, a chaotic state and finally a turbulent state for $Ra>10^5$. The study suggests that the large-scale circulation in the turbulent state is a residual of the cell structure near the onset of convection, which is in contrast with the case of $Pr\sim 1$, where the cell structure is transiently replaced by high order flow modes before the emergence of the large-scale circulation in the turbulent state. The evolution of the flow state is also reflected by the heat transport characterised by the Nusselt number $Nu$ and the probability density function (p.d.f.) of the temperature fluctuation at the cell centre. It is found that the effective local heat transport scaling exponent $\gamma$, i.e. $Nu\sim Ra^{\gamma }$, changes continuously from $\gamma =0.49$ at $Ra\sim 10^4$ to $\gamma =0.25$ for $Ra>10^6$. Meanwhile, the p.d.f. at the cell centre gradually evolves from a Gaussian-like shape before the transition to turbulence to an exponential-like shape in the turbulent state. For $Ra>10^6$, the flow shows self-similar behaviour, which is revealed by the universal shape of the p.d.f. of the temperature fluctuation at the cell centre and a $Nu=0.19Ra^{0.25}$ scaling for the heat transport.

According to Hamilton's rule, matrilineal-biased investment restrains men in matrilineal societies from maximising their inclusive fitness (the ‘matrilineal puzzle'). A recent hypothesis argues that when women breed communally and share household resources, a man should help his sisters' household, rather than his wife's household, as investment to the later but not the former would be diluted by other unrelated members (Wu et al., 2013). According to this hypothesis, a man is less likely to help on his wife's farm when there are more women reproducing in the wife's household, because on average he would be less related to his wife's household. We used a farm-work observational dataset, that we collected in the matrilineal Mosuo in southwest China, to test this hypothesis. As predicted, high levels of communal breeding by women in his wife's households do predict less effort spent by men on their wife's farm, and communal breeding in men's natal households do not affect whether men help on their natal farms. Thus, communal breeding by women dilutes the inclusive fitness benefits men receive from investment to their wife and children, and may drive the evolution of matrilineal-biased investment by men. These results can help solve the ‘matrilineal puzzle'.

Sepsis is a clinical syndrome characterised by a severe disorder of pathophysiology caused by infection of pathogenic micro-organisms. The addition of antioxidant micronutrient therapies such as thiamine to sepsis treatment remains controversial. This study explored the effect of thiamine on the prognosis of patients with sepsis. This study was a retrospective study involving patients with sepsis from the Medical Information Mart for Intensive Care IV. Patients were divided into two groups, the thiamine received group (TR) and the thiamine unreceived group (TUR), according to whether they were supplemented with thiamin via intravenous while in the intensive care unit (ICU). The primary outcome was ICU mortality. The association between thiamine and outcome was analysed using the Cox proportional hazards regression model, propensity score matching (PSM), generalised boosted model-based inverse probability of treatment weighting (IPTW) and doubly robust estimation. A total of 11 553 sepsis patients were enrolled in this study. After controlling for potential confounders using Cox regression models, the TR group had a statistically significantly lower ICU mortality risk than the TUR group. The hazard ratio of ICU mortality for the TR group was 0·80 (95 % CI 0·70, 0·93). We obtained the same results after using PSM, IPTW and doubly robust estimation. Supplementation with thiamine has a beneficial effect on the prognosis of patients with sepsis. More randomised controlled trials are needed to confirm the effectiveness of thiamine supplementation in the treatment of sepsis.