Formation of Inorganic Sulfate and Volatile Nonsulfated Products from Heterogeneous Hydroxyl Radical Oxidation of 2-Methyltetrol Sulfate Aerosols: Mechanisms and Atmospheric Implications.

Chemical transformation of 2-methyltetrol sulfates (2-MTS), key isoprene-derived secondary organic aerosol (SOA) constituents, through heterogeneous hydroxyl radical (•OH) oxidation can result in the formation of previously unidentified atmospheric organosulfates (OSs). However, detected OSs cannot fully account for the sulfur content released from reacted 2-MTS, indicating the existence of sulfur in forms other than OSs such as inorganic sulfates. This work investigated the formation of inorganic sulfates through heterogeneous •OH oxidation of 2-MTS aerosols. Remarkably, high yields of inorganic sulfates, defined as the moles of inorganic sulfates produced per mole of reacted 2-MTS, were observed in the range from 0.48 ± 0.07 to 0.68 ± 0.07. These could be explained by the production of sulfate (SO4 •-) and sulfite (SO3 •-) radicals through the cleavage of C-O(S) and (C)O-S bonds, followed by aerosol-phase reactions. Additionally, nonsulfated products resulting from bond cleavage were likely volatile and evaporated into the gas phase, as evidenced by the observed aerosol mass loss (≤25%) and concurrent size reduction upon oxidation. This investigation highlights the significant transformation of sulfur from its organic to inorganic forms during the heterogeneous oxidation of 2-MTS aerosols, potentially influencing the physicochemical properties and environmental impacts of isoprene-derived SOAs.

Which intervention is optimal to control blood glucose and improve physical performance in the elderly living with type 2 diabetes mellitus? A network meta-analysis.

BACKGROUND AND OBJECTIVES: This study aimed to find the optimal intervention available to both control blood glucose and improve physical function in the geriatric population with T2DM. METHODS AND STUDY DESIGN: A systemic review and network meta-analysis (NMA) was conducted to assess and rank the comparative efficacy of different interventions on glycosylated hemoglobin A1c (HbAc1), fasting blood glucose (FBG), muscle mass, grip strength, gait speed, lower body muscle strength, and dynamic balance. A total of eight databases were searched for eligible randomized controlled trials (RCTs) that the elderly aged more than 60 years or with mean age ≥ 55 years, the minimal duration of the RCT intervention was 6 weeks, and those lacking data about glycemic level and at least one indicator of physical performance were excluded. The Cochrane risk of bias tool was used to assess the bias of each study included. Bayesian NMA was performed as the main results, the Bayesian meta regression and the frequentist NMA as sensitivity analysis. RESULTS: Of the 2266 literature retrieved, 27 RCTs with a total of 2289 older adults were included. Health management provided by health workers exerts beneficial effects that is superior to other interventions at achieving glycemic control, but less marked improvement in physical performance. Exercise combined with cognitive training showed more pronounced improvement in muscle strength, gait speed, and dynamic balance, but ranked behind in decreasing the HbAc1 and FBG. CONCLUSIONS: Personalized health management combined with physical and cognitive training might be the optimal intervention to both accomplish glycemic control and improvement of physical performance. Further RCTs are needed to validate and assess the confidence of our results from this NMA.

A New Tissue Engineering Strategy to Promote Tendon-bone Healing: Regulation of Osteogenic and Chondrogenic Differentiation of Tendon-derived Stem Cells.

In the field of sports medicine, repair surgery for anterior cruciate ligament (ACL) and rotator cuff (RC) injuries are remarkably common. Despite the availability of relatively effective treatment modalities, outcomes often fall short of expectations. This comprehensive review aims to thoroughly examine current strategies employed to promote tendon-bone healing and analyze pertinent preclinical and clinical research. Amidst ongoing investigations, tendon-derived stem cells (TDSCs), which have comparatively limited prior exploration, have garnered increasing attention in the context of tendon-bone healing, emerging as a promising cell type for regenerative therapies. This review article delves into the potential of combining TDSCs with tissue engineering methods, with ACL reconstruction as the main focus. It comprehensively reviews relevant research on ACL and RC healing to address the issues of graft healing and bone tunnel integration. To optimize tendon-bone healing outcomes, our emphasis lies in not only reconstructing the original microstructure of the tendon-bone interface but also achieving proper bone tunnel integration, encompassing both cartilage and bone formation. In this endeavor, we thoroughly analyze the transcriptional and molecular regulatory variables governing TDSCs differentiation, incorporating a retrospective analysis utilizing single-cell sequencing, with the aim of unearthing relevant signaling pathways and processes. By presenting a novel strategy rooted in TDSCs-driven osteogenic and chondrogenic differentiation for tendon-bone healing, this study paves the way for potential future research avenues and promising therapeutic applications. It is anticipated that the findings herein will contribute to advancing the field of tendon-bone healing and foster the exploration of TDSCs as a viable option for regenerative therapies in the future.

An ex vivo method to evaluate vasoactivity induced by hemoglobin-based oxygen carriers in resistance vessels.

Red blood cell substitutes offer a solution to the problem of blood shortage and side effects of blood transfusion. Hemoglobin-based oxygen carriers (HBOCs) are one of the promising substitutes for red blood cells. Vasoactivity, which refers to the side effect of HBOCs that causes vasoconstriction and subsequent hypertension, limits the clinical application of HBOCs. In this study, an ex vivo method for the evaluation of vasoactivity induced by HBOCs was established based on isolated rat mesenteric artery vessels and the DMT120CP system. The DMT120CP system, equipped with a flowmeter, permits the control of intravascular pressure, pressure gradient, and flow conditions with high accuracy, simulating the physiological conditions for isolated vessels. The concentration of noradrenaline was optimized to 1 × 10-6∼3 × 10-6 M. PEGylated bovine hemoglobin (PEG-bHb) was synthesized and perfused into the vessel for vasoactivity evaluation, with bHb as the positive control and PSS buffer solution as the negative control. PEG-bHb showed a hydration diameter of 15.5 ± 1.4 nm and a P50 value of 6.99 mmHg. PEG-bHb exhibited a colloid osmotic pressure of 64.1 mmHg and a viscosity of 1.73 cp at 40 mg/mL. The established vasoactivity evaluation method showed significant differences in samples (bHb or PEG-bHb) with different vasoactivity properties. The vasoconstriction percentage induced by PEG-bHb samples synthesized in different batches showed coefficients of variation less than 5%, indicating good applicability and repeatability. The established evaluation method can be applied to study the vasoactivity induction and elimination strategies, promoting the clinical application of HBOCs.

Decreases in Epoxide-Driven Secondary Organic Aerosol Production under Highly Acidic Conditions: The Importance of Acid-Base Equilibria.

Isoprene has the highest atmospheric emissions of any nonmethane hydrocarbon, and isoprene epoxydiols (IEPOX) are well-established oxidation products and the primary contributors forming isoprene-derived secondary organic aerosol (SOA). Highly acidic particles (pH 0-3) widespread across the lower troposphere enable acid-driven multiphase chemistry of IEPOX, such as epoxide ring-opening reactions forming methyltetrol sulfates through nucleophilic attack of sulfate (SO42-). Herein, we systematically demonstrate an unexpected decrease in SOA formation from IEPOX on highly acidic particles (pH < 1). While IEPOX-SOA formation is commonly assumed to increase at low pH when more [H+] is available to protonate epoxides, we observe maximum SOA formation at pH 1 and less SOA formation at pH 0.0 and 0.4. This is attributed to limited availability of SO42- at pH values below the acid dissociation constant (pKa) of SO42- and bisulfate (HSO4-). The nucleophilicity of HSO4- is 100× lower than SO42-, decreasing SOA formation and shifting particulate products from low-volatility organosulfates to higher-volatility polyols. Current model parameterizations predicting SOA yields for IEPOX-SOA do not properly account for the SO42-/HSO4- equilibrium, leading to overpredictions of SOA formation at low pH. Accounting for this underexplored acidity-dependent behavior is critical for accurately predicting SOA concentrations and resolving SOA impacts on air quality.

Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.

Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.

Applying a Phase-Separation Parameterization in Modeling Secondary Organic Aerosol Formation from Acid-Driven Reactive Uptake of Isoprene Epoxydiols under Humid Conditions.

Secondary organic aerosol (SOA) from acid-driven reactive uptake of isoprene epoxydiols (IEPOX) contributes up to 40% of organic aerosol (OA) mass in fine particulate matter. Previous work showed that IEPOX substantially converts particulate inorganic sulfates to surface-active organosulfates (OSs). This decreases aerosol acidity and creates a viscous organic-rich shell that poses as a diffusion barrier, inhibiting additional reactive uptake of IEPOX. To account for this "self-limiting" effect, we developed a phase-separation box model to evaluate parameterizations of IEPOX reactive uptake against time-resolved chamber measurements of IEPOX-SOA tracers, including 2-methyltetrols (2-MT) and methyltetrol sulfates (MTS), at ~ 50% relative humidity. The phase-separation model was most sensitive to the mass accommodation coefficient, IEPOX diffusivity in the organic shell, and ratio of the third-order reaction rate constants forming 2-MT and MTS ( k M T / k M T S ). In particular, k M T / k M T S had to be lower than 0.1 to bring model predictions of 2-MT and MTS in closer agreement with chamber measurements; prior studies reported values larger than 0.71. The model-derived rate constants favor more particulate MTS formation due to 2-MT likely off-gassing at ambient-relevant OA loadings. Incorporating this parametrization into chemical transport models is expected to predict lower IEPOX-SOA mass and volatility due to the predominance of OSs.

Disparate nonlinear neural dynamics measured with different techniques in macaque and human V1.

Diverse neuro-imaging techniques measure different aspects of neural responses with distinct spatial and temporal resolutions. Relating measured neural responses across different methods has been challenging. Here, we take a step towards overcoming this challenge, by comparing the nonlinearity of neural dynamics measured across methods. We used widefield voltage-sensitive dye imaging (VSDI) to measure neural population responses in macaque V1 to visual stimuli with a wide range of temporal waveforms. We found that stimulus-evoked VSDI responses are surprisingly near-additive in time. These results are qualitatively different from the strong sub-additive dynamics previously measured using fMRI and electrocorticography (ECoG) in human visual cortex with a similar set of stimuli. To test whether this discrepancy is specific to VSDI-a signal dominated by subthreshold neural activity, we repeated our measurements using widefield imaging of a genetically encoded calcium indicator (GcaMP6f)-a signal dominated by spiking activity, and found that GCaMP signals in macaque V1 are also near-additive. Therefore, the discrepancies in the extent of sub-additivity between the macaque and the human measurements are unlikely due to differences between sub- and supra-threshold neural responses. Finally, we use a simple yet flexible delayed normalization model to capture these different dynamics across measurements (with different model parameters). The model can potentially generalize to a broader set of stimuli, which aligns with previous suggestion that dynamic gain-control is a canonical computation contributing to neural processing in the brain.

MiR-653-5p drives osteoarthritis pathogenesis by modulating chondrocyte senescence.

BACKGROUND: Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression. METHODS: We screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus. RESULTS: MiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice. CONCLUSIONS: MiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.

Dexmedetomidine Prolongs Lidocaine Intravenous Regional Anesthesia in Rats by Blocking the Hyperpolarization-Activated Cation Current.

Purpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons. Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation. Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.

Neural correlates of perceptual similarity masking in primate V1.

Visual detection is a fundamental natural task. Detection becomes more challenging as the similarity between the target and the background in which it is embedded increases, a phenomenon termed 'similarity masking'. To test the hypothesis that V1 contributes to similarity masking, we used voltage sensitive dye imaging (VSDI) to measure V1 population responses while macaque monkeys performed a detection task under varying levels of target-background similarity. Paradoxically, we find that during an initial transient phase, V1 responses to the target are enhanced, rather than suppressed, by target-background similarity. This effect reverses in the second phase of the response, so that in this phase V1 signals are positively correlated with the behavioral effect of similarity. Finally, we show that a simple model with delayed divisive normalization can qualitatively account for our findings. Overall, our results support the hypothesis that a nonlinear gain control mechanism in V1 contributes to perceptual similarity masking.

No Difference in Bone Tunnel Enlargement and Clinical Outcome between Cortical Suspension and Hybrid Femoral Fixation in Hamstring Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. METHODS: From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side-to-side difference by the KT-1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow-up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2-test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t-test, and the Mann-Whitney U-test was undertaken between the two groups without normal distribution. RESULTS: Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient-reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient-reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. CONCLUSIONS: No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.

Mesoscopic calcium imaging in a head-unrestrained male non-human primate using a lensless microscope.

Mesoscopic calcium imaging enables studies of cell-type specific neural activity over large areas. A growing body of literature suggests that neural activity can be different when animals are free to move compared to when they are restrained. Unfortunately, existing systems for imaging calcium dynamics over large areas in non-human primates (NHPs) are table-top devices that require restraint of the animal's head. Here, we demonstrate an imaging device capable of imaging mesoscale calcium activity in a head-unrestrained male non-human primate. We successfully miniaturize our system by replacing lenses with an optical mask and computational algorithms. The resulting lensless microscope can fit comfortably on an NHP, allowing its head to move freely while imaging. We are able to measure orientation columns maps over a 20 mm2 field-of-view in a head-unrestrained macaque. Our work establishes mesoscopic imaging using a lensless microscope as a powerful approach for studying neural activity under more naturalistic conditions.

Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization.

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research. Methods: We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1. Results: Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10-3), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed. Conclusions: The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.

Tapered Fiber Bioprobe Based on U-Shaped Fiber Transmission for Immunoassay.

In this paper, a tapered fiber bioprobe based on Mach-Zehnder interference (MZI) is proposed. To retain the highly sensitive straight-tapered fiber MZI sensing structure, we designed a U-shaped transmission fiber structure for the collection of optical sensing signals to achieve a miniature-insert-probe design. The spectrum responses from the conventional straight-tapered fiber MZI sensor and our proposed sensor were compared and analyzed, and experimental results showed that our proposed sensor not only has the same sensing capability as the straight-tapered fiber sensor, but also has the advantages of being flexible, convenient, and less liquid-consuming, which are attributed to the inserted probe design. The tapered fiber bioprobe obtained a sensitivity of 1611.27 nm/RIU in the refractive index detection range of 1.3326-1.3414. Finally, immunoassays for different concentrations of human immunoglobulin G were achieved with the tapered fiber bioprobe through surface functionalization, and the detection limit was 45 ng/mL. Our tapered fiber bioprobe has the insert-probe advantages of simpleness, convenience, and fast operation. Simultaneously, it is low-cost, highly sensitive, and has a low detection limit, which means it has potential applications in immunoassays and early medical diagnosis.

Heterogeneous Oxidation Products of Fine Particulate Isoprene Epoxydiol-Derived Methyltetrol Sulfates Increase Oxidative Stress and Inflammatory Gene Responses in Human Lung Cells.

Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous ·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by ·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2, and CAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by ·OH exposure was associated with an increased expression of glutathione pathway-related genes (GCLM and GCLC) and an anti-inflammatory gene (IL-10).

Environmental carcinogen benzo[a]pyrene alters neutral lipid storage via a cyp-35A2 mediated pathway in Caenorhabditis elegans.

Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.

Nonequilibrium Behavior in Isoprene Secondary Organic Aerosol.

Recent studies have shown that instantaneous gas-particle equilibrium partitioning assumptions fail to predict SOA formation, even at high relative humidity (∼85%), and photochemical aging seems to be one driving factor. In this study, we probe the minimum aging time scale required to observe nonequilibrium partitioning of semivolatile organic compounds (SVOCs) between the gas and aerosol phase at ∼50% RH. Seed isoprene SOA is generated by photo-oxidation in the presence of effloresced ammonium sulfate seeds at <1 ppbv NOx, aged photochemically or in the dark for 0.3-6 h, and subsequently exposed to fresh isoprene SVOCs. Our results show that the equilibrium partitioning assumption is accurate for fresh isoprene SOA but breaks down after isoprene SOA has been aged for as short as 20 min even in the dark. Modeling results show that a semisolid SOA phase state is necessary to reproduce the observed particle size distribution evolution. The observed nonequilibrium partitioning behavior and inferred semisolid phase state are corroborated by offline mass spectrometric analysis on the bulk aerosol particles showing the formation of organosulfates and oligomers. The unexpected short time scale for the phase transition within isoprene SOA has important implications for the growth of atmospheric ultrafine particles to climate-relevant sizes.

Elliptically polarized light photoelasticity based on LCD.

We propose a three-wavelength elliptically polarized light photoelasticity method for high efficiency and low-cost stress measurement. By illuminating the sample with two different forms of elliptically polarized light for each wavelength sources, twelve images are acquired. From these images, phase delay and the principal internal stress difference are precisely computed using developed algorithms. Our proposed method based on an LCD panel has the unrivalled advantage that elliptically polarized light can be automatically adjusted, which reduces the mechanical rotation of the system, in contrast to the traditional six-step phase-shifting photoelasticity method, which requires manual rotation for circularly polarized light. In addition, the system has the potential to theoretically expand the area of illumination infinitely, thereby expanding the measurement area. The viability of the suggested methods is confirmed with numerical simulation and stress measurement.

Cefmetazole sodium as an allosteric effector that regulates the oxygen supply efficiency of adult hemoglobin.

Allosteric effectors play an important role in regulating the oxygen supply efficiency of hemoglobin for blood storage and disease treatment. However, allosteric effectors that are approved by the US FDA are limited. In this study, cefmetazole sodium (CS) was found to bind adult hemoglobin (HbA) from FDA library (1338 compounds) using surface plasmon resonance imaging high-throughput screening. Using surface plasmon resonance (SPR), the interaction between CS and HbA was verified. The oxygen dissociation curve of HbA after CS interaction showed a significant increase in P50 and theoretical oxygen-release capacity. Acid-base sensitivity (SI) exhibited a decreasing trend, although not significantly different. An oxygen dissociation assay indicated that CS accelerated HbA deoxygenation. Microfluidic modulated spectroscopy showed that CS changed the ratio of the alpha-helix to the beta-sheet of HbA. Molecular docking suggested CS bound to HbA's ß-chains via hydrogen bonds, with key amino acids being N282, K225, H545, K625, K675, and V544.The results of molecular dynamics simulations (MD) revealed a stable orientation of the HbA-CS complex. CS did not significantly affect the P50 of bovine hemoglobin, possibly due to the lack of Valß1 and Hisß2, indicating that these were the crucial amino acids involved in HbA's oxygen affinity. Competition between the 2,3-Diphosphoglycerate (2,3-DPG) and CS in the HbA interaction was also determined by SPR, molecular docking and MD. In summary, CS could interact with HbA and regulate the oxygen supply efficiency via forming stable hydrogen bonds with the ß-chains of HbA, and showed competition with 2,3-DPG.Communicated by Ramaswamy H. Sarma.