Evaluation of Renal Microhemodynamics Heterogeneity in Different Strains and Sexes of Mice.

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor ß among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.

Sub-cycle strong-field tunneling dynamics in solids.

Tunneling ionization is a crucial process in the interaction between strong laser fields and matter which initiates numerous nonlinear phenomena including high-order harmonic generation, photoelectron holography, etc. Both adiabatic and nonadiabatic tunneling ionization are well understood in atomic systems. However, the tunneling dynamics in solids, especially nonadiabatic tunneling, has not yet been fully understood. Here, we study the sub-cycle resolved strong-field tunneling dynamics in solids via a complex saddle-point method. We compare the instantaneous momentum at the moment of tunneling and the tunneling distances over a range of Keldysh parameters. Our results demonstrate that for nonadiabatic tunneling, tunneling ionization away from Γ point is possible. When this happens the electron has a nonzero initial velocity when it emerges in the conduction band. Moreover, consistent with atomic tunneling, a reduced tunneling distance as compared to the quasi-static case is found. Our results provide remarkable insight into the basic physics governing the sub-cycle electron tunneling dynamics with significant implications for understanding subsequent strong-field nonlinear phenomena in solids.

Harnessing the benefits of glycine supplementation for improved pancreatic microcirculation in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.

Control of the electron dynamics in solid-state high harmonic generation on ultrafast time scales by a polarization-skewed laser pulse.

Since high-order harmonic generation (HHG) from atoms depends sensitively on the polarization of the driving laser field, the polarization gating (PG) technique was developed and applied successfully to generate isolated attosecond pulses from atomic gases. The situation is, however, different in solid-state systems as it has been demonstrated that due to collisions with neighboring atomic cores of the crystal lattice strong HHG can be generated even by elliptically- and circularly-polarized laser fields. Here we apply PG to solid-state systems and find that the conventional PG technique is inefficient for the generation of isolated ultrashort harmonic pulse bursts. In contrast, we demonstrate that a polarization-skewed laser pulse is able to confine the harmonic emission to a time window of less than one-tenth of the laser cycle. This method provides a novel way to control HHG and to generate isolated attosecond pulses in solids.

Separating Daily 1 km PM2.5 Inorganic Chemical Composition in China since 2000 via Deep Learning Integrating Ground, Satellite, and Model Data.

Fine particulate matter (PM2.5) chemical composition has strong and diverse impacts on the planetary environment, climate, and health. These effects are still not well understood due to limited surface observations and uncertainties in chemical model simulations. We developed a four-dimensional spatiotemporal deep forest (4D-STDF) model to estimate daily PM2.5 chemical composition at a spatial resolution of 1 km in China since 2000 by integrating measurements of PM2.5 species from a high-density observation network, satellite PM2.5 retrievals, atmospheric reanalyses, and model simulations. Cross-validation results illustrate the reliability of sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) estimates, with high coefficients of determination (CV-R2) with ground-based observations of 0.74, 0.75, 0.71, and 0.66, and average root-mean-square errors (RMSE) of 6.0, 6.6, 4.3, and 2.3 µg/m3, respectively. The three components of secondary inorganic aerosols (SIAs) account for 21% (SO42-), 20% (NO3-), and 14% (NH4+) of the total PM2.5 mass in eastern China; we observed significant reductions in the mass of inorganic components by 40-43% between 2013 and 2020, slowing down since 2018. Comparatively, the ratio of SIA to PM2.5 increased by 7% across eastern China except in Beijing and nearby areas, accelerating in recent years. SO42- has been the dominant SIA component in eastern China, although it was surpassed by NO3- in some areas, e.g., Beijing-Tianjin-Hebei region since 2016. SIA, accounting for nearly half (∼46%) of the PM2.5 mass, drove the explosive formation of winter haze episodes in the North China Plain. A sharp decline in SIA concentrations and an increase in SIA-to-PM2.5 ratios during the COVID-19 lockdown were also revealed, reflecting the enhanced atmospheric oxidation capacity and formation of secondary particles.

Transcriptome Analysis of the Developmental Effects of Bisphenol F Exposure in Chinese Medaka (Oryzias sinensis).

Bisphenol F (BPF) has been used in the syntheses of polymers, which are widely used in coatings, varnishes, adhesives, and other plastics. During the past decades, BPF contamination in the aquatic environment has dramatically increased due to its release from manmade products. Concerns have driven much attention to whether it may adversely impact aquatic lives or human beings. The present study performed an acute toxic exposure experiment and a 15 d developmental exposure of BPF at environmental concentrations (20, 200, and 2000 ng/L) using Chinese medaka (Oryzias sinensis). In the acute toxic exposure, the LC50 of BPF to Chinese medaka is 87.90 mg/L at 96 h. Developmental exposure induced a significant increase in the frequency of larvae with abnormalities in the 2000 ng/L BPF group compared to the control group. Transcriptomic analysis of the whole larvae revealed 565 up-regulated and 493 down-regulated genes in the 2000 ng/L BPF exposure group. Analysis of gene ontology and KEGG pathways enrichments indicated endocrine disorders to be associated with BPF-induced developmental toxicity. The present results suggest that BPF is developmentally toxic at 2000 ng/L concentration in Chinese medaka and causes endocrine-related aberrations in the transcriptional network of genes.

Probing Resonant Photoionization Time Delay by Self-Referenced Molecular Attoclock.

Attosecond time-resolved electron tunneling dynamics have been investigated by using attosecond angular streaking spectroscopy, where a clock reference to the laser field vector is required in atomic strong-field ionization and the situation becomes complicated in molecules. Here we reveal a resonant ionization process via a transient state by developing an electron-tunneling-site-resolved molecular attoclock in Ar-Kr^{+}. Two distinct deflection angles are observed in the photoelectron angular distribution in the molecular frame, corresponding to the direct and resonant ionization pathways. We find the electron is temporally trapped in the Coulomb potential wells of the Ar-Kr^{+} before finally releasing into the continuum when the electron tunnels through the internal barrier. By utilizing the direct tunneling ionization as a self-referenced arm of the attoclock, the time delay of the electron trapped in the resonant state is revealed to be 3.50±0.04 fs. Our results give an impetus to exploring the ultrafast electron dynamics in complex systems and also endow a semiclassical presentation of the electron trapping dynamics in a quantum resonant state.

Effects of a ketogenic diet in women with PCOS with different uric acid concentrations: a prospective cohort study.

RESEARCH QUESTION: Do overweight/obese women with PCOS with different uric acid concentrations show different effects after a ketogenic diet intervention? DESIGN: The study involved women with PCOS with a body mass index (BMI) of ≥24 kg/m2. Groups showing different uric acid concentrations were given ketogenic diet guidance for 12 weeks. Weight, BMI, body fat percentage, fasting blood glucose, triacylglyerols, total cholesterol, uric acid and other metabolism-related indexes were measured. RESULTS: After 12 weeks of the ketogenic diet intervention, body weight (hyperuricaemia group: P=0.001; non-hyperuricaemia group: P<0.001), BMI (hyperuricaemia group: P = 0.025; non-hyperuricaemia group: P<0.001) and body fat percentage (hyperuricaemia group: P<0.001; non-hyperuricaemia group: P<0.001) were decreased in both groups. There was greater weight loss in the non-hyperuricaemia group (hyperuricaemia group 11.2±4.6 kg versus non-hyperuricaemia group 14.7±4.8 kg; P < 0.05). In the non-hyperuricaemia group, uric acid concentrations increased significantly after 6 weeks of the ketogenic diet intervention (week 0: 5.69±0.84 mg/dl versus week 6: 8.41 ± 2.33 mg/dl; P < 0.001) and reached the concentrations of the hyperuricaemia group (week 6: 9.37 ± 2.43 mg/dl; P > 0.05). CONCLUSIONS: A ketogenic diet intervention is beneficial for overweight/obese women with PCOS with different serum uric acid concentrations. Participants with normal basal uric acid concentrations showed a greater fluctuation of serum uric acid concentrations during the ketogenic diet intervention and had a greater weight loss.

Correlation between home systolic blood pressure variability and cognitive impairment in maintenance hemodialysis patients.

INTRODUCTION: To investigate the correlation between home blood pressure variability and cognitive function in maintenance hemodialysis (MHD) patients. METHODS: Patients who received MHD were included. Their home blood pressure on nondialysis days within 1 week was collected. All patients were assessed with the Montreal Cognitive Assessment scale, according to which the patients were divided into cognitive impairment (CI) group and non-CI group, and the differences between two groups were compared. RESULTS: A total of 224 patients were included in the study, of which 168 had CI (75%). Compared with non-CI group, patients in CI group had larger variability of systolic blood pressure (SBPV) (8.4 [6.7, 10.6]% vs. 6.9 [4.9, 8.8]%, P < 0.001). The smooth fitting curve (OR = 1.2, 95% CI [1.1-1.4], P < 0.001) and trend test (P for trend = 0.004) showed that the risk of CI raised with the increase of SBPV. The patients were further divided into tertiles according to the SBPV. We also found a gradual increase in the proportion of incident CI in the three tertiles. Multiple logistic regression analysis showed that age, shorter years of education, less frequency of hemodialysis, and greater SBPV were the dependent risk of CI. CONCLUSION: In conclusion, greater SBPV indicates higher risk of cognitive impairment in MHD patients.

Cost-effectiveness analysis of newborn screening by tandem mass spectrometry in Shenzhen, China: value and affordability of new screening technology.

BACKGROUND: Newborn screening (NBS) can prevent inborn errors of metabolism (IEMs), which may cause long-term disability and even death in newborns. However, in China, tandem mass spectrometry (MS/MS) screening has just started. This study aimed to assess the cost-effectiveness of NBS using MS/MS in Shenzhen under the nationally recommended program, as well as evaluate the value and affordability of introducing this new screening technology. METHODS: A Markov model was built to estimate the cost and quality-adjusted life-years (QALYs) of different screening programs. We compared PKU screening using traditional immunofluorescence (IF) with the other 11 IEMs not screened and all 12 IEMs screened using MS/MS, and the programs detecting different numbers of IEMs chosen from the national recommended program were also compared. A sensitivity analysis and budget impact analysis (BIA) were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) of detecting all 12 IEMs in the national program is 277,823 RMB per QALY, below three times per capita GDP in Shenzhen. MS/MS screening in Shenzhen can be cost-effective only if at least three diseases (PKU, PCD and MMA) are covered and when the screening program covers five diseases (PKU, PCD, MMA, MSUD, IVA), the ICER closely approaches its critical threshold. The BIA indicated the implementation cost of the national program to be around 490 million RMB over 10 years and showed no difference in budget between programs detecting different numbers of IEMs. CONCLUSIONS: We conclude that the newborn screening using MS/MS in Shenzhen is cost-effective, and the budget affordable for the Shenzhen government. Two concepts for selecting the IEMs to be detected are also presented. One is to choose the most cost-effective screening programs detecting highest number of IEMs to achieve a minimal ICER. The other considers the curability and affordability of the disease as the basis of healthcare decisions to screen suitable IEMs, achieving an ICER under the threshold and close to the minimum value.