cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.

BACKGROUND: Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL. METHODS: Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia. RESULTS: Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products. CONCLUSIONS: A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.

17ß-estradiol activates SOX6 to balance the anabolism and catabolism via estrogen receptor 2 in chondrocyte.

We investigated the influence of 17ß-estradiol (17ß-E2) on cartilage extracellular matrix (ECM) homeostasis in postmenopausal women. We focused on the roles of estrogen receptors (ESR) and SOX6 in 17ß-E2-mediated stimulation of ECM metabolism during chondrocyte (CH) degeneration. We compared the expression of anabolic genes (collagen II and aggrecan) and catabolic genes (MMPs and TIMPs) in IL-1ß-induced CH degeneration in vitro, with and without 17ß-E2 supplementation. We separately silenced the SOX6, ESR1, and ESR2 genes in CHs to determine their impact on 17ß-E2 treatment. Additionally, we used Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and luciferase assays to investigate protein-DNA interactions within ESR2 and SOX6-promoter complexes. After three days of IL-1ß treatment, ESR1/2, SOX6, collagen II, aggrecan, and TIMP1/3 were decreased, while MMP3/9/13 were increased. The addition of 17ß-E2 partially reversed these effects, but silencing SOX6, ESR1, or ESR2 weakened the protective effects of 17ß-E2. Silencing ESR2, but not ESR1, abolished the upregulation of SOX6 induced by 17ß-E2. ESR2 was found to bind the SOX6 promoter and regulate SOX6 expression. 17ß-E2 upregulates SOX6 through ESR2 mediation, and the synergistic effect of 17ß-E2 and ESR2 on SOX6 balances ECM metabolism in CHs.

Mn(II) Coordination Complex Loaded Hydrogel: Synthesis, Characterization, Fluorescence Properties, and Application in Treating Knee Arthritis.

Using a mixed-ligand approach, we successfully obtained two Mn(II)-based coordination compounds, namely [Mn2(L1)(TBIP)·H2O]n (1) and [Mn2(L2)(NPTA)·H2O]n (2) (where L1 and L2 are 1,4-bis(thiabenzimidazol-1-ylmethyl)benzene and 1,2-bis(thiabenzimidazol-1-ylmethyl)benzene, H2NPTA is 2-nitroterephthalic acid, and H2TBIP is 5-tert-butylisophthalic acid). Fluorescence performance testing of complexes 1 and 2 showed excellent green and blue fluorescence properties. Based on this, we further prepared HA/CMCS hydrogels using natural polysaccharides hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials and studied their internal structural characteristics using scanning electron microscopy. Using "Duhuo Jisheng Decoction" as a drug model, two metal gel scaffolds loaded with "Duhuo Jisheng Decoction" were prepared, and their potential for treating knee osteoarthritis was evaluated.

A novel hydrangea-like magnetic composite Fe3O4@MnO2@ZIF-67 for efficient selective adsorption of Pd(II) from metallurgical wastewater.

The selective adsorption of palladium from wastewater is a feasible solution to solving palladium pollution and resource scarcity. Because traditional solvent extraction methods often involve the use of considerable amounts of organic solvents, research is focused on investigating adsorption techniques that can selectively remove palladium from wastewater. In this paper, the magnetic composite Fe3O4@MnO2@ZIF-67 was synthesized and its performance for the adsorption of Pd(II) in acidic water was investigated. Fe3O4@MnO2@ZIF-67 was characterized by various analytical methods such as TEM, SEM, EDS, BET, XRD, FTIR, zeta potential analysis, VSM, and TGA. The effects of palladium ion concentration, contact time, pH, and temperature on adsorption were evaluated. The kinetics were shown to follow the pseudo-second-order kinetic model and Elovich model, and the rate-limiting step was chemisorption. Thermodynamic studies showed that increasing the temperature promoted the adsorption of Pd(II), and the maximum uptake capacity of Fe3O4@MnO2@ZIF-67 for Pd(II) was 531.91 mg g-1. Interestingly, Fe3O4@MnO2@ZIF-67 exhibited superior selectivity for Pd(II) in the presence of Ir(IV), Pt(IV), and Rh(III). The adsorbent can be used repeatedly for selective adsorption of palladium. Even at the fifth cycle, the uptake rate of Pd(II) remained as high as 83.1%, and it showed a favorable adsorption capacity and selectivity for Pd(II) in real metallurgical wastewater. The adsorption mechanism was analyzed by SEM, FTIR, XRD, XPS, and DFT calculations, which indicated that electrostatic interactions and coordination with nitrogen-containing groups were involved. Fe3O4@MnO2@ZIF-67 is a promising adsorbent for the efficient adsorption and selective separation of palladium ions.

Mechanism Analysis of Discharge Energy in the Electrostatic-Field-Induced Electrolyte Jet Micro-EDM.

The discharge energy determines the machining resolution, minimum processable feature size, and surface roughness, which makes it a hot research topic in the microelectrical discharge machining (EDM) field. In this paper, a kind of novel discharge-energy-generation method in micro-EDM is investigated. In this method, the opposite induced charges on the electrolyte jet and workpiece serve as the source of the discharge energy. The operating mechanism of this discharge energy is revealed by analyzing the equivalent discharge circuit. The unique discharge current and voltage between the electrolyte jet and the workpiece are sampled and investigated. In contrast with the pulsating energy in conventional EDM, this study shows that the direct current (DC) voltage source can automatically generate a continuously periodical pulsating discharge in the electrostatic-field-induced electrolyte jet (E-Jet) EDM process. After further analyzing the electric signals in a single discharge process, it can be found that the interelectrode voltage experienced a continuous sharp electric breakdown, a nearly unchanging process, and a fast exponential recharging process. The discharge frequency increases as the electrolyte concentration and interelectrode voltage increase but decreases as the interelectrode distance increases. The discharge energy per pulse increases with the increasing interelectrode distance and electrolyte concentration but with the decreasing interelectrode voltage. Finally, the electrostatic-field-induced discharge-energy generation and change mechanisms are revealed, which provides a feasible method for micro-EDM with continuous tiny pulsed energy only using the DC power supply.

Research on Electrostatic Field-Induced Discharge Energy in Conventional Micro EDM.

The electrostatic field-induced electrolyte jet (E-Jet) electric discharge machining (EDM) is a newly developed micro machining method. However, the strong coupling of the electrolyte jet liquid electrode and the electrostatic induced energy prohibited it from utilization in conventional EDM process. In this study, the method with two discharge devices connecting in serials is proposed to decouple pulse energy from the E-Jet EDM process. By automatic breakdown between the E-Jet tip and the auxiliary electrode in the first device, the pulsed discharge between the solid electrode and the solid workpiece in the second device can be generated. With this method, the induced charges on the E-Jet tip can indirectly regulate the discharge between the solid electrodes, giving a new pulse discharge energy generation method for traditional micro EDM. The pulsed variation of current and voltage generated during the discharge process in conventional EDM process verified the feasibility of this decoupling approach. The influence of the distance between the jet tip and the electrode, as well as the gap between the solid electrode and the work-piece, on the pulsed energy, demonstrates that the gap servo control method is applicable. Experiments with single points and grooves indicate the machining ability of this new energy generation method.

Outstanding Performance of the Deep Eutectic Solvent-Based Aqueous Biphasic System Constructed with Sodium Citrate for a Green Gold Separation.

Aqueous biphasic systems (ABSs) that are based on deep eutectic solvents (DESs) are environmentally benign systems to use for metal ion separation. In this work, a series of DESs was synthesized for the first time with PEG 400 as hydrogen bond donors and tetrabutylphonium bromide (P4Br), tetrabutylammonium bromide (N4Br), or tetrabutylammonium chloride (N4Cl) as hydrogen bond acceptors, and then they were combined with citrate (Na3C6H5O7), which is eco-friendly, to construct an ABS for use in the separation of Au(I) from an aurocyanide solution. Phase diagrams of DESs + Na3C6H5O7 + H2O systems were constructed using the experimentally measured data. Multiple factors that affect the efficiency of the gold extraction were studied; these factors were the species of salt or DES and their content, the equilibrium pH, the oscillation time, and the initial gold concentration. Gold(I) is preferentially retained in the DES-rich phase, and the P4Br:PEG 1:2 + Na3C6H5O7 + H2O system has a high extraction efficiency of 100.0% under optimized conditions. FT-IR, NMR, and TEM characterizations and DFT calculations show that the migration of Au(I) from the salt-rich to the DES-rich phase follows an ion exchange mechanism. Specifically, Au(CN)2- replaces Br- in the original P4Br and generates a stable ion pair with the quaternary phosphonium salt cation, P+, and this replacement is driven by electrostatic attractions. A new strong hydrogen bond network simultaneously forms between the anionic Au(CN)2- and the -OH group in the PEG 400 component. Finally, the gold of Au(I)-loaded P4Br:PEG 1:2 can be successfully reduced by sodium borohydride with an efficiency of 100.0%. The strategy to extract gold(I) from alkaline cyanide solutions using an ABS based on DESs as proposed in this work provides a potential platform for developing green technology for recovering gold.

Characteristics and Functional Application of Cellulose Fibers Extracted from Cow Dung Wastes.

The widespread use of petroleum-based products has led to increasing environmental and ecological problems, while the extraction and application of various natural cellulose fibers have received increasing attention. This research focuses on the extraction of cellulose fibers from cow dung using different treatments: hot water, hydrogen peroxide (H2O2), sodium hydroxide (NaOH) and potassium hydroxide (KOH) boilings, as well as a selection of the best quality cow dung fibers for papermaking with quality control. The study's objective is to find a sustainable method to extract as much material as possible from renewable biomass feedstock. The results show that the best extraction rate is obtained by KOH boiling with 42% cellulose fibers extracted. Corresponding handmade paper has a burst index of 2.48 KPam2/g, a tear index of 4.83 mNm2/g and a tensile index of 26.72 Nm/g. This project expands the sources of natural cellulose fibers to an eco-friendly and sustainable one and opens up new applications for cow dung.

A multifunctional adsorbent based on 2,3-dimercaptosuccinic acid/dopamine-modified magnetic iron oxide nanoparticles for the removal of heavy-metal ions.

Overexploitation of nature by humans has led to an increasingly serious issue of heavy-metal water pollution. To reduce the threat of water pollution to humans and the environment, it is imperative to develop or improve the water treatment technology for heavy-metal-containing wastewater. Functionalized Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) have been widely used as effective adsorbents for the removal of heavy-metal ions from water owing to their high efficiency, low cost, selective adsorption ability, and recyclability. In this study, Fe3O4@DA-DMSA magnetic nanoparticles (FDDMs) were prepared by the functionalization of Fe3O4 MNPs with environmentally friendly dopamine (DA) and a heavy-metal detoxifying agent such as 2,3-dimercaptosuccinic acid (DMSA) for the efficient and rapid adsorption of Pb2+, Cu2+, and Cd2+, with maximum adsorption capacities of 187.62, 63.01, and 49.46 mg/g, respectively. FDDMs exhibited the best ability to remove Pb2+ with a maximum adsorption capacity than that of the most reported Fe3O4 MNP-related adsorbents. In actual wastewater and multi-component simulated water samples contaminated with Pb2+, Cu2+, and Cd2+, the as-prepared adsorbent maintained a good removal ability for Pb2+ with low influence by ionic strength and interfering ions, as well as exhibited an excellent selectivity. According to the results of batch experiments and X-ray photoelectron spectroscopy (XPS) analysis of the adsorbent before and after adsorption, the adsorption mechanism of the adsorbent for the removal of heavy-metal ions mainly involves coordination and ion exchange. In addition, the adsorbent exhibited a good regeneration performance. Therefore, FDDMs can be considered as a promising adsorbent for the treatment of heavy-metal wastewater.

Kaempferol ameliorates in-vitro and in-vivo postovulatory oocyte ageing in mice.

RESEARCH QUESTION: Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity? DESIGN: The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo. RESULTS: Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%). CONCLUSIONS: Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed.

Surface modification of the Ti surface with nanoscale bio-MOF-1 for improving biocompatibility and osteointegration in vitro and in vivo.

Biocompatibility and osteointegration of implants are highly desired in orthopedic and dentistry applications. The synthesis of a coating with ideal biocompatibility and osteogenic effect carries practical significance for improving the bio-inertness of pure Ti implants. Metal-organic frameworks (MOFs) are effective surface modification agents in bone regeneration applications. Bio-MOF-1, a classic type of biofriendly MOF with a bio-derived constitution, possesses biocompatibility and osteogenic potential resulting from its Zn core and adenine ligand. In this study, bio-MOF-1 coatings at multiple concentrations were synthesized on alkali-heat treated Ti, and their cytocompatibility and osteogenic properties were systematically examined both in vitro and in vivo. Coatings were characterized to confirm the successful synthesis of bio-MOF-1 coatings. These coatings exhibited advanced thermostability, excellent biocompatibility, and stable Zn2+ release, which up-regulated the expression of osteogenesis-related genes and proteins. Furthermore, bio-MOF-1 coating of Ti implants enhanced early osseointegration at the bone-implant interface. This study demonstrates the promising potential of bio-MOF-1 coatings with the osteogenic effect for surface modification in bone tissue engineering.

Simultaneous measurement of energy spectrum and fluence of neutrons using a diamond detector.

Due to the excellent radiation hardness and high-temperature endurance, diamond detectors are suitable for intense neutron measurements and promising for neutron diagnostics of scientific fusion devices. In the present work, simultaneous measurement of energy spectrum and fluence of neutrons using a diamond detector was realized for the first time. The absolute response matrix of the diamond detector was simulated based on detailed analysis of the nuclear reactions and the proper selection of nuclear reaction data. Neutron energy spectra as well as neutron fluences for 5.0, 5.5, 8.5, 9.5 and 10.5 MeV neutrons from d-d reaction were measured using the diamond detector based on the absolute response matrix. The measured neutron energy spectra and neutron fluences are reasonable compared with those detected using a EJ-309 liquid scintillator and a 238U fission chamber, respectively, which verifies the reliability of the present work. Furthermore, the energy spectrum and fluence of a 14.2 MeV d-t neutron source were also measured using the diamond detector. The present work demonstrates the ability of simultaneous measurement of energy spectrum and fluence as well as for both d-d and d-t neutrons using a diamond detector, which is of great significance for neutron diagnostics of scientific fusion devices.

Substitute for polyethylene (PE) films: A novel cow dung-based liquid mulch on silage cornfields.

To prevent soil pollution caused by polyethylene (PE) films in the central region of Gansu, China, liquid mulching made from cow dung (CDLM) was trailed in silage maize fields. The degradation of CDLM and PE films, soil temperature, soil organic matter content, silage maize yield and water use efficiency (WUE) were evaluated for three years (2018-2020). The degradability of CDLM has been found to be much stronger than the one of PE films, with CDLM degrading 40-60 days after sowing and finishing around 100 days. CDLM had a lower insulating impact than PE films but a higher insulating effect than non-mulching films as the control (CK); CDLM could successfully increase soil organic matter, with a total increase of 1.01% over three years. CDLM increased silage maize yield by 6.2% compared to PE films and 17.2% compared to CK. Consequently, CDLM may be an interesting alternative to PE films for enhancing silage maize yield while decreasing soil contamination.

High-performance lanthanum-based metal-organic framework with ligand tuning of the microstructures for removal of fluoride from water.

Excess fluoride in water poses a threat to ecology and human health, which has attracted global attention. In this study, a series of lanthanum-based metal-organic frameworks (La-MOFs) were synthesized by varying the organic ligands (i.e., terephthalic acid (BDC), trimesic acid (BTC), biphenyl-4,4-dicarboxylic acid (BPDC), 2,5-dihydroxyterephthalic acid (BHTA), and 1,2,4,5-benzenetetracarboxylic acid (PMA)) to control the microscopic structure of the MOFs and subsequently apply them for the removal of fluoride in water. The maximum capture capacities of La-BTC, La-BPDC, La-BHTA, La-PMA, and La-BDC at 298 K are 105.2, 125.9, 145.5, 158.9, and 171.7 mg g-1, respectively. The adsorption capacity is greater than most reported adsorbents. The adsorption isotherms of La-MOFs for fluoride are well fit to the Langmuir isotherm model. In addition, the adsorption kinetics of La-BTC, La-BPDC, La-BHTA, La-PMA, and La-BDC follows the pseudo-second-order kinetic model, and the kinetic rate-limiting step of adsorption is chemical adsorption. Thermodynamics revealed that temperature is favorable for the adsorption of fluoride. Meanwhile, La-BTC, La-BPDC, La-BHTA, La-PMA, and La-BDC are suitable for the removal of fluoride in a relatively wide pH range (4.0-9.0). Simultaneously, from X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analysis, electrostatic attraction and ligand exchange are identified as the main action mechanisms for the adsorption of fluoride of La-MOFs. The prepared La-MOFs are used as efficient adsorbents for removal of fluoride in actual water, indicating that they have great potential in removing fluoride in real and complex environmental water. This work provides a new strategy for designing adsorbents with adjustable microstructure and expected function to effectively recover fluorosis in water.

Cerium-doped MIL-101-NH2(Fe) as superior adsorbent for simultaneous capture of phosphate and As(V) from Yangzonghai coastal spring water.

A series of novel cerium-doped MIL-101-NH2 materials were synthesized using the solvothermal method for the simultaneous efficient removal of phosphate and As(V). According to the characterization results, cerium was successfully loaded onto MIL-101-NH2 and that Ce-MOFs might be generated during the loading process, which modified the crystal structure of MIL-101-NH2 and resulted in MOFs with different microstructures. In single-uptake systems containing only phosphate or As(V), isothermal adsorption experiments showed that 1Ce-MIL-101-NH2 exhibited better adsorption properties of phosphate and As(V) than MIL-101-NH2. Furthermore, the uptake amounts of phosphate and As(V) reached 341.5 mg/g and 249 mg/g, respectively. Superior uptake amounts for binary phosphate (167.36 mg/g) and As(V) (87.55 mg/g) were achieved with 1Ce-MIL-101-NH2. Kinetic experiments revealed a higher uptake rate of phosphate than of As(V). FT-IR and XPS analyses showed that the main mechanism for the removal of phosphate and As(V) from water by 1Ce-MIL-101-NH2 was the formation of an Fe/CeOP inner complex through ligand complexation and electrostatic attraction. Furthermore, 1Ce-MIL-101-NH2 exhibited high selectivity and excellent efficiency in removing phosphate and As(V) in contaminated spring water in the presence of competing anions; this further confirms the application potential of the novel adsorbent.

The Application of Polycaprolactone in Three-Dimensional Printing Scaffolds for Bone Tissue Engineering.

Bone tissue engineering commonly encompasses the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the propagation of cells to regenerate damaged tissues or organs. 3D printing technology has been extensively applied to allow direct 3D scaffolds manufacturing. Polycaprolactone (PCL) has been widely used in the fabrication of 3D scaffolds in the field of bone tissue engineering due to its advantages such as good biocompatibility, slow degradation rate, the less acidic breakdown products in comparison to other polyesters, and the potential for loadbearing applications. PCL can be blended with a variety of polymers and hydrogels to improve its properties or to introduce new PCL-based composites. This paper describes the PCL used in developing state of the art of scaffolds for bone tissue engineering. In this review, we provide an overview of the 3D printing techniques for the fabrication of PCL-based composite scaffolds and recent studies on applications in different clinical situations. For instance, PCL-based composite scaffolds were used as an implant surgical guide in dental treatment. Furthermore, future trend and potential clinical translations will be discussed.

Perfluorodecanoic acid induces meiotic defects and deterioration of mice oocytes in vitro.

Perfluorodecanoic acid (PFDA) is a member of the perfluoroalkyl substances, which are toxic to organic functions. Recently, it has been found in follicular fluid, seriously interfering with reproduction. Follicular fluid provides the oocyte with necessary resources during the process of oocytes maturation. However, the effects of PFDA on the oocyte need investigation. Our study evaluated the impacts of PFDA on the meiosis and development potential of mouse oocytes by exposing oocytes to PFDA in vitro at 350, 400, and 450 µM concentrations. The results showed that exposure to PFDA resulted in the first meiotic prophase arrest by obstructing the function of the maturation-promoting factor. It also induced the dysfunction of the spindle assembly checkpoint, expedited the progression of the first meiotic process, and increased the risk of aneuploidy. The oocytes treated with PFDA had a broken cytoskeleton which also contributed to meiotic maturation failure. Besides, PFDA exposure caused mitochondria defections, increased the reactive oxygen species level in oocytes, and consequently induced oocyte apoptosis. Moreover, PFDA produced epigenetic modifications in oocytes and increased the frequency of mature oocytes with declined development potential. In summary, our data indicated that PFDA disturbs the meiotic process and induces oocyte quality deterioration.

Retrobulbar blood flow in rat eyes during acute elevation of intraocular pressure.

Most studies of the effect of acute elevation of intraocular pressure (IOP) on ocular blood-flow have utilized optical coherence tomography (OCT) to characterize retinal and choroidal flow and vascular density. This study investigates the effect of acute IOP elevation on blood flow velocity in the retrobulbar arteries and veins supplying and draining the eye, which, unlike the retinal and choroidal vasculature, are not directly compressed as IOP is increased. By cannulation of the anterior chamber of 20 Sprague-Dawley rats, we increased IOP in 10 mmHg steps from 10 to 60 mmHg and returned to 10 mmHg. After 1 min at each IOP (and 3 min after return to 10 mmHg), we acquired 18 MHz plane-wave ultrasound data at 3000 compound images/sec for 1.5 s. We produced color-flow Doppler images by digital signal processing of the ultrasound data, identified retrobulbar arteries and veins, generated spectrograms depicting flow velocity over the cardiac cycle and characterized changes of vascular density and perfusion in the orbit overall. Systolic, diastolic and mean velocities and resistive and pulsatile indices were determined from arterial spectrograms at each IOP level. Baseline mean arterial and mean venous velocities averaged 30.9 ±â€¯10.8 and 8.5 ±â€¯3.3 mm/s, respectively. Arterial velocity progressively decreased and resistance indices increased at and above an IOP of 30 mmHg. Mean arterial velocity at 60 mmHg dropped by 55% with respect to baseline, while venous velocity decreased by 20%. Arterial and venous velocities and resistance returned to near baseline after IOP was restored to 10 mmHg. Both vascular density and orbital perfusion decreased with IOP, but while perfusion returned to near normal when IOP returned to 10 mmHg, density remained reduced. Our findings are consistent with OCT-based studies showing reduced perfusion of the retina at levels comparable to retrobulbar arterial flow velocity change with increased IOP. The lesser effect on venous flow is possibly attributable to partial collapse of the venous lumen as volumetric venous outflow decreased at high IOP. The continued reduction in orbital vascular density 3 min after restoration of IOP to 10 mmHg might be attributable to persisting narrowing of capillaries, but this needs to be verified in future studies.

Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma.

Retinal ganglion cells (RGCs) expanding from the retina to the brain are primary victims of neurodegeneration in glaucoma, a leading cause of blindness; however, the neighboring astroglia survive the glaucoma-related stress and promote neuroinflammation. In light of diverse functions of caspase-8 in apoptosis, cell survival, and inflammation, this study investigated the importance of caspase-8 in different fates of glaucomatous RGCs and astroglia using two experimental approaches in parallel. In the first approach, cell type-specific responses of RGCs and astroglia to a caspase-8 cleavage-inhibiting pharmacological treatment were studied in rat eyes with or without experimentally induced glaucoma. The second approach utilized an experimental model of glaucoma in mice in which astroglial caspase-8 was conditionally deleted by cre/lox. Findings of these experiments revealed cell type-specific distinct processes that regulate caspase-8 functions in experimental glaucoma, which are involved in inducing the apoptosis of RGCs and promoting the survival and inflammatory responses of astroglia. Deletion of caspase-8 in astroglia protected RGCs against glia-driven inflammatory injury, while the inhibition of caspase-8 cleavage inhibited apoptosis in RGCs themselves. Various caspase-8 functions impacting both RGC apoptosis and astroglia-driven neuroinflammation may suggest the multi-target potential of caspase-8 regulation to provide neuroprotection and immunomodulation in glaucoma.

Association between Serum Calcium and First Incident Acute Myocardial Infarction: A Cross-Sectional Study.

BACKGROUND: The role of serum calcium in coronary artery disease (CAD) patients with or without first incident acute myocardial infarction has not been studied previously. This study aimed to assess the relationship between serum calcium and first incident acute myocardial infarction. METHODS: This cross-sectional study was conducted from Jan 2014 to Dec 2016. All the participants were from our database, described in detail elsewhere including 1609 cases and 3252 controls. Multiple logistic regression was carried out to explore the effect of serum calcium on first incident acute myocardial infarction. Interaction between serum calcium and risk factors were evaluated. RESULTS: Patients with first incident acute myocardial infarction have significantly lower serum calcium concentrations than those without acute myocardial infarction (2.18 (0.21) vs 2.24 (0.19) mmol/L, P<0.0001). After adjusting for sex and age, logistic regression showed that serum calcium was significantly associated with first incident acute myocardial infarction (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.41-1.60). Further adjusted for potential confounders, serum calcium was associated with first incident acute myocardial infarction (OR: 1.32, 95% CI: 1.22-1.42). Moreover, the association still existed when patients were divided into subgroups according to gender and age. A significant interaction was found between serum calcium and diabetes mellitus (DM), lipoprotein (a) (Lp (a)), and serum albumin. CONCLUSION: Serum calcium was associated with first incident acute myocardial infarction among CAD patients in both sexes and in age categories. This study provides further evidence showing the value of serum calcium levels in clinical practice.