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.

Clinical features of patients undergoing hemodialysis with COVID-19.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.

Histopathology and transcriptome reveals the tissue-specific hepatotoxicity and gills injury in mosquitofish (Gambusia affinis) induced by sublethal concentration of triclosan.

Triclosan (TCS), a ubiquitous antimicrobial agent, has been frequently detected in wild fish, leading to concerns regarding TCS safety in the aquatic environment. The present work aims to investigate the TCS-mediated effects on various tissues (the liver, gills, brain, and testes) of wild-sourced adult mosquitofish based on histological analysis and transcriptome. Severe morphological injuries were only found in the liver and gills. The histopathological alterations in the liver were characterized by cytoplasmic vacuolation and degeneration, eosinophilic cytoplasmic inclusions, and nuclear polymorphism. The gill lesions contained epithelial lifting, intraepithelial edema, fusion and shortening of the secondary lamellae. Consistently, the numbers of differently expressed genes (DEGs) identified by transcriptome were in the order of liver (1627) > gills (182) > brain (9) > testes (4). Trend-aligned histopathological and transcriptomic changes in the 4 tissues, suggesting the tissue-specific response manner of mosquitofish to TCS, and the liver and gills were the target organs. TCS interrupted many biological pathways associated with lipogenesis and lipid metabolism, transmembrane transporters, protein synthesis, and carbohydrate metabolism in the liver, and it induced nonspecific immune response in the gills. TCS-triggered hepatotoxicity and gills damnification may lead to inflammation, apoptosis, diseases, and even death in mosquitofish. TCS showed moderate acute toxicity and bioaccumulative property on mosquitofish, suggesting that prolonged or massive use of TCS may pose an ecological risk.

Deep Learning for Feynman's Path Integral in Strong-Field Time-Dependent Dynamics.

Feynman's path integral approach is to sum over all possible spatiotemporal paths to reproduce the quantum wave function and the corresponding time evolution, which has enormous potential to reveal quantum processes in the classical view. However, the complete characterization of the quantum wave function with infinite paths is a formidable challenge, which greatly limits the application potential, especially in the strong-field physics and attosecond science. Instead of brute-force tracking every path one by one, here we propose a deep-learning-performed strong-field Feynman's formulation with a preclassification scheme that can predict directly the final results only with data of initial conditions, so as to attack unsurmountable tasks by existing strong-field methods and explore new physics. Our results build a bridge between deep learning and strong-field physics through Feynman's path integral, which would boost applications of deep learning to study the ultrafast time-dependent dynamics in strong-field physics and attosecond science and shed new light on the quantum-classical correspondence.

Tubal choriocarcinoma presented as ruptured ectopic pregnancy: a case report and review of the literature.

BACKGROUND: Tubal choriocarcinoma is an extremely rare but highly malignant trophoblastic tumor, which may be either gestational or non-gestational in origin. Due to atypical clinical manifestations and symptoms similar to ectopic pregnancy, it is easily to be confused with ectopic pregnancy. In addition, inadequate understanding of this rare disease by clinicians often leads to misdiagnosis or missed diagnosis, which in turn results in delayed treatment or even tumor metastasis. CASE PRESENTATION: This report summarized a case of a woman who was finally diagnosed as tubal choriocarcinoma through the follow-up of serum ß hCG levels and histopathological results after undergoing salpingectomy for being misdiagnosed as ectopic pregnancy. Five courses of adjuvant chemotherapy (5-fluorouracil, actinomycin-D, vinorelbine regime) have been administered to the patient in the prevention of any recurrences. During 1-year follow-up, the patient was asymptomatic and presented no evidence of recurrence. CONCLUSIONS: Tubal choriocarcinoma is easily to be confused with ectopic pregnancy. By analyzing this case and previous related cases, we aimed to provide references for clinicians in the diagnosis and treatment of tubal choriocarcinoma.

Attosecond temporal confinement of interband excitation by intraband motion.

High order harmonic generation (HHG) in semiconductors opens a new frontier in strong field physics and attosecond science. However, the underlying physical mechanisms are not yet fully understood and lively debated. Here, we identify and discuss carrier-wave population transfer as a novel and important dynamical effect. We find that the interband excitation occurs in an extremely short time window due to the intraband motion. Our analysis based on this finding allows for a physically intuitive interpretation of the anomalous carrier-envelope phase dependence observed in HHG from MgO and to understand the dominant role of the interband polarization as reported in a series of recent semiconductor HHG experiments. Motivated by the discovered coupling mechanism, we demonstrate that the interband excitation can be controlled by an appropriately tailored two-color field. An ultrabroad supercontinuum spectrum covering the entire plateau region can be generated which directly creates an isolated-attosecond pulse even without phase compensation. Our results provide remarkable insight into the basic physics governing the sub-cycle electron motion with significant implications for the generation of isolated-attosecond light pulses in semiconductor materials.

Serum klotho: a potential predictor of cerebrovascular disease in hemodialysis patients.

BACKGROUND: Hemodialysis patients suffer from a serious threat of cerebrovascular disease. Klotho, as an aging-suppressor gene, contributes to protect on vascular calcification and oxidative stress, which are the risk factors of cerebrovascular disease. The purpose of the present study is to determine the relationship between serum klotho and cerebrovascular disease in patients receiving hemodialysis. METHODS: Serum klotho levels of hemodialysis patients were measured by ELISA. Cerebrovascular diseases were diagnosed by CT or MRI scans. The cognitive function of hemodialysis patients with cerebrovascular disease were evaluated with a neuropsychological battery assessing domains of global cognition verbal memory, spatial memory, executive function and verbal fluency. RESULTS: Eighty-eight patients were included, 57 ± 14 years, 63.64% male, 52.27% older than 60 years. Twenty-eight participants had cerebrovascular disease (23 cases had cerebral infarction, 5 cases had cerebral hemorrhage). The average level of serum klotho of all participants was 119.10 ± 47.29 pg/ml. The serum klotho level was significantly associated with cerebrovascular disease in hemodialysis patients (HR(95%CI) = 0.975(0.960-0.990), p = 0.001). The optimal cut-off value of serum klotho for predicting cerebrovascular disease in hemodialysis patients was 137.22 pg/ml, with a specificity of 96.4% and a sensitivity of 46.7%. But serum klotho was not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease (HR((95%CI) = 1.002(0.986-1.018), p = 0.776) or with cerebral infarction (HR(95%CI) = 1.005(0.987-1.023), p = 0.576). CONCLUSIONS: The serum klotho level is a potential predictor of cerebrovascular disease in hemodialysis patients, but it is not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease.

Immunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models.

Background: Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain. Methods: We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains. Results: Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-α/ß receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Conclusions: Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.

Attosecond Time Delay of Retrapped Resonant Ionization.

A recent ultrafast pump-probe technique has allowed measurement of time delays during photoemission in a variety of systems ranging from atoms and molecules to solids with unprecedented temporal resolution. However, identifying the underlying physics is still a challenge especially in complicated multichannel above-threshold ionization (ATI) experiments. Here we demonstrate that the time delays of different ionization pathways in ATI can be clearly resolved and extracted with a semiclassical statistical method. The remarkable phase shift of near threshold photoelectrons can be attributed to a temporary retrapping of a photoelectron by the atomic potential in a quasibound state after emerging in the continuum state. This continuum-bound-continuum scattering manifests as a new resonant effect in strong-field photoemission. Our results unify the seemingly opposing quantum Eisenbud-Wigner-Smith time delay and classical Coulomb-induced time delay by highlighting the same physical picture, which holds promise for an intuitive interpretation of time-resolved fundamental electronic processes in strong-field experiments and epistemological reexamination of the quantum-classical correspondence.

Direction-tunable enhanced emission from a subwavelength metallic double-nanoslit structure.

Controlling light emission out of subwavelength nanoslit/aperture structures is of great important for highly integrated photonic circuits. Here we propose a new method to achieve direction-tunable emission based on a compact metallic microcavity with double nanoslit. Our method combines the principles of Young's interference and surface plasmon polaritons interference. We show that the direction of the far-field beam can be controlled over a wide range of angles by manipulating the frequency and relative phase of light arriving at the two slits, which holds promise for applications in the ultracompact optoelectronic devices.

Calcium-dependent phospholipase A2 modulates infection-induced diaphragm dysfunction.

Calpain activation contributes to the development of infection-induced diaphragm weakness, but the mechanisms by which infections activate calpain are poorly understood. We postulated that skeletal muscle calcium-dependent phospholipase A2 (cPLA2) is activated by cytokines and has downstream effects that induce calpain activation and muscle weakness. We determined whether cPLA2 activation mediates cytokine-induced calpain activation in isolated skeletal muscle (C2C12) cells and infection-induced diaphragm weakness in mice. C2C12 cells were treated with the following: 1) vehicle; 2) cytomix (TNF-α 20 ng/ml, IL-1ß 50 U/ml, IFN-γ 100 U/ml, LPS 10 µg/ml); 3) cytomix + AACOCF3, a cPLA2 inhibitor (10 µM); or 4) AACOCF3 alone. At 24 h, we assessed cell cPLA2 activity, mitochondrial superoxide generation, calpain activity, and calpastatin activity. We also determined if SS31 (10 µg/ml), a mitochondrial superoxide scavenger, reduced cytomix-mediated calpain activation. Finally, we determined if CDIBA (10 µM), a cPLA2 inhibitor, reduced diaphragm dysfunction due to cecal ligation puncture in mice. Cytomix increased C2C12 cell cPLA2 activity (P < 0.001) and superoxide generation; AACOCF3 and SS31 blocked increases in superoxide generation (P < 0.001). Cytomix also activated calpain (P < 0.001) and inactivated calpastatin (P < 0.01); both AACOCF3 and SS31 prevented these changes. Cecal ligation puncture reduced diaphragm force in mice, and CDIBA prevented this reduction (P < 0.001). cPLA2 modulates cytokine-induced calpain activation in cells and infection-induced diaphragm weakness in animals. We speculate that therapies that inhibit cPLA2 may prevent diaphragm weakness in infected, critically ill patients.