Mechanism of CO2 in promoting the hydrogenation of levulinic acid to γ-valerolactone catalyzed by RuCl3 in aqueous solution.

A Ru-containing complex shows good catalytic performance toward the hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) with the assistance of organic base ligands (OBLs) and CO2. Herein, we report the competitive mechanisms for the hydrogenation of LA to GVL, 4-oxopentanal (OT), and 2-methyltetrahydro-2,5-furandiol (MFD) with HCOOH or H2 as the H source catalyzed by RuCl3 in aqueous solution at the M06/def2-TZVP, 6-311++G(d,p) theoretical level. Kinetically, the hydrodehydration of LA to GVL is predominant, with OT and MFD as side products. With HCOOH as the H source, initially, the OBL (triethylamine, pyridine, or triphenylphosphine) is responsible for capturing H+ from HCOOH, leading to HCOO- and [HL]+. Next, the Ru3+ site is in charge of sieving H- from HCOO-, yielding [RuH]2+ hydride and CO2. Alternatively, with H2 as the H source, the OBL stimulates the heterolysis of H-H bond with the aid of Ru3+ active species, producing [RuH]2+ and [HL]+. Toward the [RuH]2+ formation, H2 as the H source exhibits higher activity than HCOOH as the H source in the presence of an OBL. Thereafter, H- in [RuH]2+ gets transferred to the unsaturated C site of ketone carbonyl in LA. Afterwards, the Ru3+ active species is capable of cleaving the C-OH bond in 4-hydroxyvaleric acid, yielding [RuOH]2+ hydroxide and GVL. Subsequently, CO2 promotes Ru-OH bond cleavage in [RuOH]2+, forming HCO3- and regenerating the Ru3+-active species owing to its Lewis acidity. Lastly, between the resultant HCO3- and [HL]+, a neutralization reaction occurs, generating H2O, CO2, and OBLs. Thus, the present study provides insights into the promotive roles of additives such as CO2 and OBLs in Ru-catalyzed hydrogenation.

Spectral-Spatial Feature Fusion for Hyperspectral Anomaly Detection.

Hyperspectral anomaly detection is used to recognize unusual patterns or anomalies in hyperspectral data. Currently, many spectral-spatial detection methods have been proposed with a cascaded manner; however, they often neglect the complementary characteristics between the spectral and spatial dimensions, which easily leads to yield high false alarm rate. To alleviate this issue, a spectral-spatial information fusion (SSIF) method is designed for hyperspectral anomaly detection. First, an isolation forest is exploited to obtain spectral anomaly map, in which the object-level feature is constructed with an entropy rate segmentation algorithm. Then, a local spatial saliency detection scheme is proposed to produce the spatial anomaly result. Finally, the spectral and spatial anomaly scores are integrated together followed by a domain transform recursive filtering to generate the final detection result. Experiments on five hyperspectral datasets covering ocean and airport scenes prove that the proposed SSIF produces superior detection results over other state-of-the-art detection techniques.

Increased GABA signaling in liver macrophage promotes HBV replication in HBV-carrier mice.

Gamma-aminobutyric acid (GABA) signals in various non-neuronal cells including hepatocytes and some immune cells. Studies, including ours, show that type A GABA receptors (GABAARs)-mediated signaling occurs in macrophages regulating tissue-specific functions. Our recent study reveals that activation of GABAARs in liver macrophages promotes their M2-like polarization and increases HBV replication in mice. This short article briefly summarizes the GABA signaling system in macrophages and discusses potential mechanisms by which GABA signaling promotes HBV replication.

Immunologic, Anti-Inflammatory, and Anti-Muscle Damage Profile of Supplemented Vitamin D3 in Healthy Adults on Strenuous Endurance Exercise.

Reportedly, strenuous endurance exercise can depress the immune system and induce inflammation and muscle damage. Therefore, this double-blinded, matched-pair study aimed to investigate the impact of vitamin D3 supplementation on immune response (leukocyte, neutrophil, lymphocyte, CD4+, CD8+, CD19+, and CD56+ counts), inflammatory profile (TNF-α and IL-6), muscle damage (CK and LDH levels), as well as aerobic capacity after strenuous endurance exercise in 18 healthy men taking 5000 IU of vitamin D3 (n = 9) or placebo (n = 9) daily for 4 weeks. Total and differential blood leukocyte counts, levels of cytokines, and muscle damage biomarkers were determined before, immediately after, and 2, 4, and 24 h after exercise. The IL-6, CK, and LDH levels were significantly lower in vitamin D3 group at 2, 4, and 24 h post exercise (p < 0.05). Maximal and average heart rates during exercise were also significantly lower (p < 0.05). In the vitamin D3 group, the CD4+/CD8+ ratio after 4 weeks of supplementation was only significantly lower at post-0 than at baseline and significantly higher at post-2 than at baseline and post-0 (all p < 0.05). Taken together, 5000 IU of daily vitamin D3 supplementation for 4 weeks exhibited positive effects in terms of increased blood 25(OH)D levels, CD4+/CD8+ ratio (immune response), and aerobic capacity while inhibiting inflammatory cytokines and CK and LDH (muscle damage) in people performing strenuous endurance exercise.

Induction of Innate Memory in Human Monocytes Exposed to Mixtures of Bacterial Agents and Nanoparticles.

We assessed whether concomitant exposure of human monocytes to bacterial agents and different engineered nanoparticles can affect the induction of protective innate memory, an immune mechanism that affords better resistance to diverse threatening challenges. Monocytes were exposed in vitro to nanoparticles of different chemical nature, shape and size either alone or admixed with LPS, and cell activation was assessed in terms of production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). After return to baseline conditions, cells were re-challenged with LPS and their secondary "memory" response measured. Results show that nanoparticles alone are essentially unable to generate memory, while LPS induced a tolerance memory response (less inflammatory cytokines, equal or increased anti-inflammatory cytokines). LPS-induced tolerance was not significantly affected by the presence of nanoparticles during the memory generation phase, although with substantial donor-to-donor variability. This suggests that, despite the overall lack of significant effects on LPS-induced innate memory, nanoparticles may have donor-specific effects. Thus, future nanosafety assessment and nanotherapeutic strategies will need a personalized approach in order to ensure both the safety and efficacy of nano medical compounds for individual patients.

Impacts of microplastics on immunity.

Most disposable plastic products are degraded slowly in the natural environment and continually turned to microplastics (MPs) and nanoplastics (NPs), posing additional environmental hazards. The toxicological assessment of MPs for marine organisms and mammals has been reported. Thus, there is an urgent need to be aware of the harm of MPs to the human immune system and more studies about immunological assessments. This review focuses on how MPs are produced and how they may interact with the environment and our body, particularly their immune responses and immunotoxicity. MPs can be taken up by cells, thus disrupting the intracellular signaling pathways, altering the immune homeostasis and finally causing damage to tissues and organs. The generation of reactive oxygen species is the mainly toxicological mechanisms after MP exposure, which may further induce the production of danger-associated molecular patterns (DAMPs) and associate with the processes of toll-like receptors (TLRs) disruption, cytokine production, and inflammatory responses in immune cells. MPs effectively interact with cell membranes or intracellular proteins to form a protein-corona, and combine with external pollutants, chemicals, and pathogens to induce greater toxicity and strong adverse effects. A comprehensive research on the immunotoxicity effects and mechanisms of MPs, including various chemical compositions, shapes, sizes, combined exposure and concentrations, is worth to be studied. Therefore, it is urgently needed to further elucidate the immunological hazards and risks of humans that exposed to MPs.

Numerical investigation on the ranging performance of forward pulsed laser radar affected by shock waves.

When an aircraft loaded with pulsed laser radar flies at supersonic speed, the laser beam will be distorted by the uneven outflow field, resulting in a significant reduction in ranging accuracy. In this study, the influence mechanism of the shock wave on the performance of forward pulsed laser radar is investigated. First, a novel semi-analytical method is proposed to model the pulsed laser echo wave affected by shock waves, which combines the laser radar equation with optical distortion parameters. Second, an improved ray tracing method based on inverse distance-weighted interpolation with a quadrilateral mesh is proposed to trace the trajectory of the laser beam passing through the flow field, and the effectiveness and superiority of the algorithm are verified. Thereafter, an evaluation method based on the optimal confidence interval is proposed to evaluate the ranging error of pulsed laser radar; which can effectively evaluate the ranging accuracy of pulsed laser radar under the influence of the shock wave. The simulation results show that the ranging performance of pulsed laser radar below Mach 3 is slightly affected, and the detection system error and random error reach the minimum and maximum at Mach 4, respectively. This study provides a theoretical basis for the suppression of the aero-optical effect of forward pulsed laser radar at supersonic speed.

Design of a Cylindrical Compliant Linear Guide with Decoupling Parallelogram Mechanisms.

A conventional linear guiding mechanism refers to the slide rail guides composed of multiple assemble parts. These guiding mechanisms suffer from many adverse effects, including lubrication, wear and assembly issues. A novel compliant guiding mechanism is proposed in this paper to address these common problems, and this mechanism transfers or transforms motion, force and energy via the deformation of flexible members. This linear guide is designed in a cylindrical shape, and the centre platform moves along its axis (i.e., the motion direction). The proposed linear guide consists of several in-parallel curved compound double parallelogram mechanisms (CDPMs) connected by the same number of decoupling parallelogram mechanisms. Nonlinear finite element analysis (FEA) is used for stiffness analysis and shows that applying the decoupling mechanisms to the detached linear guide (the in-parallel curved CDPMs only) can dramatically improve the stiffness in undesired movement (bearing) directions while keeping its original stiffness along its axis. The nonlinear FEA can capture the stiffness variation by considering all the structural deformation. The issue of bearing-direction stiffness degradation of the detached linear guide is dealt with by applying decoupling mechanisms. The static experimental test is conducted on a 3D printed prototype and shows that the stiffness in the motion direction is nearly constant (linear). The results obtained from the experimental test show good agreement with those obtained from the nonlinear FEA with a maximum error of 9.76%.

Design of Deployable Structures by Using Bistable Compliant Mechanisms.

A deployable structure can significantly change its geometric shape by switching lattice configurations. Using compliant mechanisms as the lattice units can prevent wear and friction among multi-part mechanisms. This work presents two distinctive deployable structures based on a programmable compliant bistable lattice. Several novel parameters are introduced into the bistable mechanism to better control the behaviour of bistable mechanisms. By adjusting the defined geometry parameters, the programmable bistable lattices can be optimized for specific targets such as a larger deformation range or higher stability. The first structure is designed to perform 1D deployable movement. This structure consists of multi-series-connected bistable lattices. In order to explore the 3D bistable characteristic, a cylindrical deployable mechanism is designed based on the curved double tensural bistable lattice. The investigation of bistable lattices mainly involves four types of bistable mechanisms. These bistable mechanisms are obtained by dividing the long segment of traditional compliant bistable mechanisms into two equal parts and setting a series of angle data to them, respectively. The experiment and FEA simulation results confirm the feasibility of the compliant deployable structures.

Mechanism of Preferential Hydrogenation of Hydroxymethyl Group to Aldehyde Group in 5-Hydroxymethylfurfural over W2 C-Based Catalyst.

A W4 C2 cluster was used to model a W2 C catalyst with the armchair model of activated carbon support, noted as W4 C2 /AC. Over W4 C2 /AC, the mechanism for the hydrogenation of both -H2 OH and -CHO groups in 5-hydroxymethylfurfural (HMF) was theoretically studied in tetrahydrofuran at GGA-PBE/DNP level. 5-Methylfurfural was the major product from only hydrodehydration of the -CH2 OH group, whereas 2,5-dihydroxymethylfuran was the minor product from the hydrogenation of both -CH2 OH and -CHO groups. The rate-determining steps were concerned with the -C(H)2 -H bond formation for the hydrodehydration of -CH2 OH group, and the -(OH)(H)-H bond formation for the hydrogenation of -CHO group. Kinetically, W-sites promoted the hydrodehydration of -CH2 OH group and inhibited the hydrogenation of -CHO group. This stemmed from the strong Lewis acidity of W-sites, which easily accepted the lone-pair electrons of the oxygen atom in the -C(OH)(H)- group, making -C(OH)(H)-H bond formation hard, and hampering the hydrogenation of the -CHO group.

Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway.

Zinc is an essential trace element that is often reduced under the type 1 diabetic condition. Previous studies demonstrated that zinc deficiency enhanced type 1 diabetes-induced liver injury and that zinc supplementation significantly helped to prevent this. Due to the differences in pathogenesis between type 1 and type 2 diabetes, it is unknown whether zinc supplementation can induce a beneficial effect on type 2 diabetes-induced liver injury. This possible protective mechanism was investigated in the present study. A high-fat diet, along with a one-time dose of streptozotocin, was applied to metallothionein (MT) knockout mice, nuclear factor-erythroid 2-related factor (Nrf) 2 knockout mice, and age-matched wild-type (WT) control mice, in order to induce type 2 diabetes. This was followed by zinc treatment at 5 mg/kg body weight given every other day for 3 months. Global metabolic disorders of both glucose and lipids were unaffected by zinc supplementation. This induced preventive effects on conditions caused by type 2 diabetes like oxidative stress, apoptosis, the subsequent hepatic inflammatory response, fibrosis, hypertrophy, and hepatic dysfunction. Additionally, we also observed that type 2 diabetes reduced hepatic MT expression, while zinc supplementation induced hepatic MT expression. This is a crucial antioxidant. A mechanistic study showed that MT deficiency blocked zinc supplementation-induced hepatic protection under the condition of type 2 diabetes. This suggested that endogenous MT is involved in the hepatic protection of zinc supplementation in type 2 diabetic mice. Furthermore, zinc supplementation-induced hepatic MT increase was unobserved once Nrf2 was deficient, indicating that Nrf2 mediated the upregulation of hepatic MT in response to zinc supplementation. Results of this study indicated that zinc supplementation prevented type 2 diabetes-induced liver injury through the activation of the Nrf2-MT-mediated antioxidative pathway.

Astaxanthin attenuates alcoholic cardiomyopathy via inhibition of endoplasmic reticulum stress-mediated cardiac apoptosis.

Chronic excessive ethanol consumption is associated with a high incidence of mortality due to ethanol-induced dilated cardiomyopathy, known as alcoholic cardiomyopathy (ACM). Mechanistic studies have demonstrated that apoptosis is key to the pathogenesis of ACM, and endoplasmic reticulum (ER) stress-associated apoptosis contributes to various ethanol-related diseases. Astaxanthin (AST) is a natural carotenoid that exerts an anti-ER stress effect. Importantly, strong evidence has shown that AST induces beneficial effects in various cardiovascular diseases. The present study aimed to investigate whether AST induces beneficial effects on ACM by suppressing cardiac apoptosis mediated by ER stress. We showed that after 2 months of chronic excessive ethanol consumption, mice displayed obvious cardiac dysfunction and morphological changes associated with increased fibrosis, oxidative stress, ER stress and apoptosis. However, cardiac damage above was attenuated in response to AST treatment. The cardioprotective effect of AST against ethanol toxicity was also confirmed in both H9c2 cells and primary cardiomyocytes, indicating that AST-induced protection directly targets cardiomyocytes. Both in vivo and in vitro studies showed that AST inhibited all three ER stress signaling pathways activated by ethanol. Furthermore, administration of the ER stress inhibitor sodium 4-phenylbutyrate (4-PBA) strongly suppressed ethanol-induced cardiomyocyte damage. Interestingly, AST induced further anti-apoptotic effects once co-treated with 4-PBA, indicating that AST protects the heart from ACM partially by attenuating ER stress, but other mechanisms still exist. This study highlights that administration of AST ablated chronic excessive ethanol consumption-induced cardiomyopathy by suppressing cardiac ER stress and subsequent apoptosis.

Therapeutic Effects of Fibroblast Growth Factor-21 on Diabetic Nephropathy and the Possible Mechanism in Type 1 Diabetes Mellitus Mice.

BACKGROUND: Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN. METHODS: Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups. RESULTS: The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression. CONCLUSION: Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.

50 mm-aperture Nd:LuAG ceramic nanosecond laser amplifier producing 10 J at 10 Hz.

The growth and laser amplifier performance of a large-aperture Nd:LuAG ceramic are reported. Using the vacuum sintering and high-temperature insostatic pressing (HIP) methods, three pieces of a 50 mm-aperture Nd:LuAG ceramic are fabricated and used as the gain medium in a diode-pumped nanosecond distributed active mirror amplifier chain (DAMAC). The energy storage capacity of large-aperture Nd:LuAG is investigated and compared with that of Nd:YAG. Energy amplification up to 10.3 J at 10 Hz is achieved, which, to the best of our knowledge, produces the highest peak power (1 GW) using Nd:LuAG. The excellent energy storage and extraction performance confirm the great potential of Nd:LuAG in high-energy scaling.

12 J, 10 Hz diode-pumped Nd:YAG distributed active mirror amplifier chain with ASE suppression.

Experimental amplification of 10-ns pulses to an energy of 12.2 J at the repetition rate of 1-10 Hz is reported from a diode-pumped room-temperature distributed active mirror amplifier chain (DAMAC) based on Nd:YAG slabs. Efficient power scaling at the optical-optical efficiency of 20.6% was achieved by suppressing the transverse parasitic oscillation with ASE absorbers. To the best of our knowledge, this is the first demonstration of a diode-pumped Nd:YAG active-mirror laser with nanosecond pulse energy beyond 10 joules. The verified DAMAC concept holds the promise of scaling the energy to a 50 J level and higher by adding 10-12 more pieces of active mirror in the chain.

Efficient sub-joule energy extraction from a diode-pumped Nd:LuAG amplifier seeded by a Nd:YAG laser.

We report on a joule-level diode-pumped Nd:YAG-Nd:LuAG hybrid active mirror amplifier chain, producing an output energy of 1.52 J at 10 Hz in a 10 ns Q-switched pulse, while a pulse energy of 623 mJ is extracted from the Nd:LuAG stage, corresponding to an optical-to-optical efficiency of 21.7%. To the best of our knowledge, this is the first demonstration of high-energy nanosecond pulse amplification in a Nd:LuAG laser with extracted pulse energies approaching the joule level. The excellent scaling performance confirms Nd:LuAG as a very promising gain medium for high-energy, short-pulse lasers.