This paper addresses the persistent ambiguity in the evaluation of legitimate expectations within investor–state dispute settlement (ISDS), critically examining this through Fuller’s interactional theory. Traditional approaches fail to adequately capture the evolving socio-economic contexts and the dynamic nature of investor–state interactions. This paper introduces a novel analytical model that integrates Fuller’s principles, emphasizing continuous dialogue and mutual understanding between investors and host states. By shifting focus from static legal interpretations to interaction-based assessments, this framework provides a more equitable and context-sensitive method for adjudicating legitimate expectations. The research offers significant academic contributions by redefining the foundational principles of legitimate expectations in ISDS, highlighting the necessity of procedural fairness and shared understanding. Practically, it proposes actionable guidelines for tribunals and policymakers to enhance the legitimacy and predictability of investment arbitration. This includes revising bilateral investment treaties (BITs) for explicit policy disclosure and fostering ongoing communication between parties. The adoption of Fuller’s interactional theory in ISDS not only clarifies legal ambiguities but also promotes a more cooperative and transparent investment climate, ultimately benefiting both investors and host states.

Immunological castration can be an alternative to traditional surgical castration. The active immunization against GnRH or kisspeptin has a castrating effect. To date, the fusion protein vaccine of combination with GnRH and kisspeptin have not been studied. Thus, the present study will develop a GnRH6-kisspeptin vaccine by genetic engineering method and investigate its immunocastration effect in male rats. Twenty 20-day-old male rats were randomly divided into two groups: the control group (n=10) and the immunization group (n=10). The initial immunization took place at week 0 followed by three booster doses administered intervals. The control group received an equivalent dose of white oil adjuvant. Orbital blood samples were collected at various time points following the initial immunization, at 0, 2, 4, 6, 8, 10 and 12 weeks, respectively. The entire left testis was weighed and its volume measured at week 12. Samples from the right testis were obtained for histological analysis. Serum levels of GnRH and kisspeptin antibodies, as well as testosterone levels were determined using ELISA. The results showed that the serum levels of GnRH and kisspeptin antibody titres of the immunized rats were significantly higher compared to the control group (P<0.05). Additionally, the testosterone concentration was effectively reduced following the intensified immunization. The testes of the immunized group exhibited a reduction in size and a significant decrease in the number of spermatogonia in the testicular tissue compared to the control group (P<0.05). These data indicate that the recombinant GnRH6-kisspeptin protein effectively induced immunological castration in rats.

Diagnostic classification models (DCMs) have seen wide applications in educational and psychological measurement, especially in formative assessment. DCMs in the presence of testlets have been studied in recent literature. A key ingredient in the statistical modeling and analysis of testlet-based DCMs is the superposition of two latent structures, the attribute profile and the testlet effect. This paper extends the standard testlet DINA (T-DINA) model to accommodate the potential correlation between the two latent structures. Model identifiability is studied and a set of sufficient conditions are proposed. As a byproduct, the identifiability of the standard T-DINA is also established. The proposed model is applied to a dataset from the 2015 Programme for International Student Assessment. Comparisons are made with DINA and T-DINA, showing that there is substantial improvement in terms of the goodness of fit. Simulations are conducted to assess the performance of the new method under various settings.

Timing of food intake is an emerging aspect of nutrition; however, there is a lack of research accurately assessing food timing in the context of the circadian system. The study aimed to investigate the relation between food timing relative to clock time and endogenous circadian timing with adiposity and further explore sex differences in these associations among 151 young adults aged 18–25 years. Participants wore wrist actigraphy and documented sleep and food schedules in real time for 7 consecutive days. Circadian timing was determined by dim-light melatonin onset (DLMO). The duration between last eating occasion and DLMO (last EO-DLMO) was used to calculate the circadian timing of food intake. Adiposity was assessed using bioelectrical impedance analysis. Of the 151 participants, 133 were included in the statistical analysis finally. The results demonstrated that associations of adiposity with food timing relative to circadian timing rather than clock time among young adults living in real-world settings. Sex-stratified analyses revealed that associations between last EO-DLMO and adiposity were significant in females but not males. For females, each hour increase in last EO-DLMO was associated with higher BMI by 0·51 kg/m2 (P = 0·01), higher percent body fat by 1·05 % (P = 0·007), higher fat mass by 0·99 kg (P = 0·01) and higher visceral fat area by 4·75 cm2 (P = 0·02), whereas non-significant associations were present among males. The findings highlight the importance of considering the timing of food intake relative to endogenous circadian timing instead of only as clock time.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Accurate online estimation of the payload parameters benefits robot control. In the existing approaches, however, on the one hand, only the linear friction model was used for online payload identification, which reduced the online estimation accuracy. On the other hand, the estimation models contain much noise because of using actual joint trajectory signals. In this article, a new estimation algorithm based on parameter difference for the payload dynamics is proposed. This method uses a nonlinear friction model for the online payload estimation instead of the traditionally linear one. In addition, it considers the commanded joint trajectory signals as the computation input to reduce the model noise. The main contribution of this article is to derive a symbolic relationship between the parameter difference and the payload parameters and then apply it to the online payload estimation. The robot base parameters without payload were identified offline and regarded as the prior information. The one with payload can be solved online by the recursive least squares method. The dynamics of the payload can be then solved online based on the numerical difference of the two parameter sets. Finally, experimental comparisons and a manual guidance application experiment are shown. The results confirm that our algorithm can improve the online payload estimation accuracy (especially the payload mass) and the manual guidance comfort.

We report a home-built velocity-gradient-tensor-resolved particle image velocimetry (VGTR-PIV) system which spatio-temporally resolves all components of the velocity gradient tensor. This technique is applied to the paradigmatic turbulent Rayleigh–Bénard convection system in a cylindrical cell at three representative positions, i.e. centre, side and bottom regions. The VGTR-PIV system allows us to directly measure, for the first time, the spatio-temporally resolved energy dissipation rate and enstrophy in turbulent thermal convection. In the experiment, the Rayleigh number $Ra$ varied in the range $2 \times 10^8 \leqslant Ra \leqslant 8 \times 10^9$ and the Prandtl number $Pr$ was fixed at $Pr = 4.34$. Compared with the fully resolved energy dissipation rate $\varepsilon$, the pseudo-dissipation provides the best estimate within $3\,\%$, the planar (two-dimensional) surrogate has a larger relative error and the one-dimensional surrogate leads to the largest error. The power-law scalings of the time-averaged energy dissipation rate with the Rayleigh number follow $\langle \varepsilon _c \rangle _t / (\nu ^3 H^{-4}) = 9.86 \times 10^{-6} Ra^{1.54 \pm 0.02}$, $\langle \varepsilon _s \rangle _t / (\nu ^3 H^{-4}) = 9.26 \times 10^{-3} Ra^{1.25 \pm 0.02}$ and $\langle \varepsilon _b \rangle _t / (\nu ^3 H^{-4}) = 2.70 \times 10^{-2} Ra^{1.23 \pm 0.02}$ in the centre, side and bottom regions, respectively where $\nu$ is dynamic viscosity and $H$ is cell height. These scaling relations, along with our earlier measured time-averaged energy dissipation rate at the bottom wall surface $\langle \varepsilon _w \rangle _t / (\nu ^3 H^{-4}) = 9.65 \times 10^{-2} Ra^{1.25 \pm 0.02}$ (J. Fluid Mech., vol. 947, 2022, A15), provide important constraints against which theoretical models may be tested. For the centre and side locations in the convection cell, the probability density functions (p.d.f.s) of the energy dissipation rate and enstrophy both follow a stretched exponential distribution. For the bottom region, the p.d.f.s of dissipation and enstrophy exhibit a stretched exponential distribution outside the viscous boundary layer and an exponential distribution inside the viscous boundary layer. It is also found that extreme events with high dissipation are the most intermittent in the side region, whereas the bottom region is less intermittent than the cell centre.

Zygotic genome activation (ZGA) is a critical event in early embryonic development, and thousands of genes are involved in this delicate and sophisticated biological process. To date, however, only a handful of these genes have revealed their core functions in this special process, and therefore the roles of other genes still remain unclear. In the present study, we used previously published transcriptome profiling to identify potential key genes (candidate genes) in minor ZGA and major ZGA in both human and mouse specimens, and further identified the conserved genes across species. Our results showed that 887 and 760 genes, respectively, were thought to be specific to human and mouse in major ZGA, and the other 135 genes were considered to be orthologous genes. Moreover, the conserved genes were most enriched in rRNA processing in the nucleus and cytosol, ribonucleoprotein complex biogenesis, ribonucleoprotein complex assembly and ribosome large subunit biogenesis. The findings of this first comprehensive identification and characterization of candidate genes in minor and major ZGA provide relevant insights for future studies on ZGA.

Salt solutions have complex effects on the swelling characteristics of compacted bentonite; these effects are caused by the inhibitory action of salinity and the ion-exchange reaction between the solution and bentonite. In order to characterize the swelling properties of compacted bentonite in a salt solution, swelling deformation tests were carried out for Gao-Miao-Zi (GMZ) bentonite specimens in NaCl and CaCl2 solutions. Swelling characteristics decreased with increasing salt concentration. Swelling strains in NaCl solution were larger than those in CaCl2 solution, even though the ionic concentration of 1.0 mol/L (M) NaCl solution is larger than that of 0.5 M CaCl2. According to the exchangeable cations tests, cation exchange was different for specimens immersed in different salt solutions. The swelling fractal model was used to predict the swelling strains of compacted bentonite in a concentrated salt solution. In this model, the effective stress incorporating osmotic suction was applied to take the effect of salinity into consideration, and the swelling coefficient, K, was employed to describe the swelling properties affected by the variation in exchangeable cations. In the model, fractal dimension was measured by nitrogen adsorption, and the salt solution had little effect on fractal dimension. K was estimated by the diffuse double layer (DDL) model for osmotic swelling in distilled water. Comparison of fractal model estimations with experimental data demonstrated that the new model performed well in predicting swelling characteristics affected by a salt solution.

Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.

Abnormalities in the zona pellucida (ZP) adversely affect oocyte maturation, embryo development and pregnancy outcomes. However, the assessment of severity is challenging. To evaluate the effects of different degrees of ZP abnormalities on embryo development and clinical outcomes, in total, 590 retrieval cycles were scored and divided into four categories (control, mild, moderate and severe) based on three parameters: perivitelline space, percentage of immature oocytes and percentage of oocytes with abnormal morphology. As the severity of abnormal ZP increased, both the number of retrieved oocytes and mature oocytes decreased. The fertilization rate did not differ significantly among groups. The rates of embryo cleavage and day-3 high-quality embryos in the mild group and the moderate group did not vary significantly between the two groups but were significantly higher than those in the severe group. The blastulation rates of the abnormal ZP groups were similar; however, they were lower than those of the control group. Moreover, the cycle cancellation rate of the severe abnormal ZP group was as high as 66.20%, which was significantly higher than that of the other three groups. Although the rates of cumulative clinical pregnancy and live births were lower than those in the control group, they were comparable among the abnormal ZP groups. There were no differences in the neonatal outcomes of the different groups. Together, ZP abnormalities show various degrees of severity, and in all patients regardless of the degree of ZP abnormalities who achieve available embryos, there will be an opportunity to eventually give birth.

Routine blood examination is an easy way to examine infectious diseases. This study is aimed to develop a model to diagnose serious bacterial infections (SBI) in ICU neonates based on routine blood parameters. This was a cross-sectional study, and data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III). SBI was defined as suffering from one of the following: pyelonephritis, bacteraemia, bacterial meningitis, sepsis, pneumonia, cellulitis, and osteomyelitis. Variables with statistical significance in the univariate logistic regression analysis and log systemic immune–inflammatory index (SII) were used to develop the model. The area under the curve (AUC) was calculated to assess the performance of the model. A total of 1,880 participants were finally included for analysis. Weight, haemoglobin, mean corpuscular volume, white blood cell, monocyte, premature delivery, and log SII were selected to develop the model. The developed model showed a good performance to diagnose SBI for ICU neonates, with an AUC of 0.812 (95% confidence interval (CI): 0.737–0.888). A nomogram was developed to make this model visualise. In conclusion, our model based on routine blood parameters performed well in the diagnosis of neonatal SBI, which may be helpful for clinicians to improve treatment recommendations.

According to the public data collected from the Health Commission of Gansu Province, China, regarding the COVID-19 pandemic during the summer epidemic cycle in 2022, the epidemiological analysis showed that the pandemic spread stability and the symptom rate (the number of confirmed cases divided by the sum of the number of asymptomatic cases and the number of confirmed cases) of COVID-19 were different among 3 main epidemic regions, Lanzhou, Linxia, and Gannan; both the symptom rate and the daily instantaneous symptom rate (daily number of confirmed cases divided by the sum of daily number of asymptomatic cases and daily number of confirmed cases) in Lanzhou were substantially higher than those in Linxia and Gannan. The difference in the food sources due to the high difference of the population ethnic composition in the 3 regions was probably the main driver for the difference of the symptom rates among the 3 regions. This work provides potential values for prevention and control of COVID-19 in different regions.

In vitro rearing of honey bee larvae is ideal for bioassay studies; no honey bee stable cell lines are available. Inconsistency of internal development staging of reared larvae and a susceptibility to contamination are common problems encountered. Standardized protocols on rearing larvae in vitro to make the larvae growth and development more similar to that of natural colonies are necessary to ensure the accuracy of experimental results and promote honey bee research as a model organism. Here, we concluded that when larval fasting weight was >160 mg, the time point of gut emptying can be defined as the critical point separating the larval and prepupal stages. In this way, we can conduct precise studies on the prepupal stage, such as organ remodeling during metamorphosis. Simultaneously, we further verified that recombinant AccApidaecin in genetic engineered bacteria added to the larval diet upregulated antibacterial peptide gene expression, and did not stimulate the stress response in larvae, nor did it affect the pupation rate or eclosion rate. This demonstrated that feeding recombinant AccApidaecin can enhance the individual antibacterial ability at the molecular level.

High-power continuous-wave ultraviolet lasers are useful for many applications. As ultraviolet laser sources, the wavelength switching capability and compact structure are very important to extend the applicability and improve the flexibility in practical applications. In this work, we present two simple and relatively compact schemes by laser diode pumping to obtain a watt-level single-wavelength 348.7-nm laser and discrete wavelength tunable ultraviolet lasers around 349 nm (from 334.7 to 364.5 nm) by intracavity frequency doubling based on Pr3+:YLF and $\unicode{x3b2}$-BBO crystals. The maximum output power of the single-wavelength 348.7-nm laser is 1.033 W. The output powers of the discrete wavelength tunable lasers are at the level of tens of milliwatts, except for two peaks at 348.7 and 360.3 nm with output powers of approximately 500 mW. In addition, simulations are carried out to explain the experimental results and clarify the tuning mechanisms.

Adolescence is a significant period for the formation of relationship networks and the development of internalizing problems. With a sample of Chinese adolescents (N = 3,834, 52.01% girls, Mage = 16.68 at Wave 1), the present study aimed to identify the configuration of adolescents’ relationship qualities from four important domains (i.e., relationship quality with mother, father, peers, and teachers) and how distinct profiles were associated with the development of internalizing problems (indicated by depressive and anxiety symptoms) across high school years. Latent profile analysis identified a five-profile configuration with four convergent profiles (i.e., relationship qualities with others were generally good or bad) and one “Father estrangement” profile (i.e., the relationship quality with others were relatively good but that with father was particularly poor). Further conditional latent growth curve analysis indicated the “Father estrangement” profile was especially vulnerable to an increase in the internalizing problems as compared with other relationship profiles. This study contributes to understanding the characteristics of interpersonal relationship qualities and their influences on adolescent internalizing problems in a non-Western context. Results were further discussed from a culturally specific perspective.