Inhibition of SK2 and ER stress ameliorated inflammation and apoptosis in liver ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) remains a major cause of mortality and morbidity after liver surgery. Endoplasmic reticulum (ER) stress is a critical mechanism of inflammatory injury during hepatic IRI. In this study, we investigated the effect of sphingosine kinases 2 (SK2) on ER stress and hepatic IRI. We established hepatic IRI mice and hepatocellular hypoxia/reoxygenation in vitro model. We observed the SK2 and ER stress protein IRE1α expression. Then, we used an SK2 inhibitor and knocked down IRE1α/SK2, to observe the effect of SK2 during IRI. Our results showed that the expression of ER stress and SK2 was significantly elevated during hepatic IRI. Inhibition of SK2 ameliorated liver inflammation and reduced cell apoptosis in hepatic IRI mice. Consistently, we found that the inhibition of IRE1α also downregulated SK2 expression and reduced mitochondrial membrane permeability. Furthermore, the knockdown of SK2 could also reduce cell damage and reduce the expression of inflammatory factors but did not influence ER stress-related signaling pathway. Taken together, our results suggested that ER stress and SK2 played important and regulatory roles in hepatic IRI. Inhibition of ER stress and SK2 could significantly improve liver function after hepatic IRI.

Tear film instability is associated with weakened colocalization between occludin and MUC5AC in scopolamine-induced dry eye disease (DED) rats.

PURPOSE: Dry eye disease (DED) is a disease with tear film instability because of multiple factors. This study was conducted to explore roles of occludin and MUC5AC in tear film instability in DED rat model. METHODS: A total of 20 SD rats were divided into DED group (n = 10) and normal control (NC) group (n = 10). DED rat model was established by subcutaneously injecting with scopolamine hydrobromide. Clinical examinations, including tear breakup time (tBUT), Schirmer's test and corneal fluorescein staining, were conducted to determine corneal functions. Transmission electron microscopy was used to measure the ultrastructures of corneal epithelial cells. Western blotting assay was used to identify occludin expression in corneal tissues of DED rats. Real-time PCR (RT-PCR) was performed to verify gene transcription of occludin and MUC5AC. Colocalization between occludin and MUC5AC was identified with confocal fluorescence microscopy. RESULTS: Tear breakup time was significantly shorter, and corneal fluorescein staining score was predominantly higher in DED rats compared to those in normal rats (P < 0.05). Normal rats showed a steady tear secretion throughout the whole experiments, while DED rats showed a dramatic reduction on day 14. DED rats demonstrated ultrastructural damage of Golgi apparatus and endoplasmic reticulum in corneal epithelial cells. Occludin and MUC5AC expressions were significantly downregulated in corneal tissue of DED rats compared with those of normal rats (P < 0.05). Percentage of occludin-MUC5AC-colocalized corneal epithelial cells in DED rats was significantly less compared with those in normal rats (P < 0.01). CONCLUSIONS: Tear film stability was damaged in scopolamine-induced DED rats because of the weakened colocalization between occludin and MUC5AC molecule. This study would provide a potential clue for the pathogenesis and a promising theoretical basis for clinical work of DED.

Sunlight-Induced Interfacial Electron Transfer of Ferrihydrite under Oxic Conditions: Mineral Transformation and Redox Active Species Production.

Fe(II)-catalyzed ferrihydrite transformation under anoxic conditions has been intensively studied, while such mechanisms are insufficient to be applied in oxic environments with depleted Fe(II). Here, we investigated expanded pathways of sunlight-driven ferrihydrite transformation in the presence of dissolved oxygen, without initial addition of dissolved Fe(II). We found that sunlight significantly facilitated the transformation of ferrihydrite to goethite compared to that under dark conditions. Redox active species (hole-electron pairs, reactive radicals, and Fe(II)) were produced from the ferrihydrite interface via the photoinduced electron transfer processes. Experiments with systematically varied wet chemistry conditions probed the relative contributions of three pathways for the production of hydroxyl radicals: (1) oxidation of water (5.0%); (2) reduction of dissolved oxygen (40.9%); and (3) photolysis of Fe(III)-hydroxyl complexes (54.1%). Results also showed superoxide radicals as the main oxidant for Fe(II) reoxidation under acidic conditions, thus promoting the ferrihydrite transformation. The presence of inorganic ions (chloride, sulfate, and nitrate) did not only affect the hydrolysis and precipitation of Fe(III) but also the generation of radicals via photoinduced charge transfer reactions. The involvement of redox active species and the accompanying mineral transformations would exert a profound effect on the fate of multivalent elements and organic contaminants in aquatic environments.

Pseudocapacitive Behaviors of Polypyrrole Grafted Activated Carbon and MnO2 Electrodes to Enable Fast and Efficient Membrane-Free Capacitive Deionization.

Capacitive deionization (CDI) has emerged as a promising technique for brackish water desalination. Here, composites of polypyrrole grafted activated carbon (Ppy/AC) were prepared via in situ chemical oxidative polymerization of pyrrole on AC particles. The Ppy/AC cathode was then coupled with a MnO2 anode for desalination in a membrane-free CDI cell. Both the Ppy/AC and MnO2 electrodes exhibited pseudocapacitive behaviors, which can selectively and reversibly intercalate Cl- (Ppy/AC) and Na+ (MnO2) ions. Compared to AC electrodes, the specific capacitances of Ppy/AC electrodes increased concurrently with the pyrrole ratios from 0 to 10%, while the charge transfer and ionic diffusion resistances decreased. As a result, the 10%Ppy/AC-MnO2 cell showed a maximum salt removal capacity of 52.93 mg g-1 (total mass of active materials) and 34.15 mg g-1 (total mass of electrodes), which was higher than those of conventional, membrane, and hybrid CDI cells. More notably, the salt removal rate of the 10%Ppy/AC-MnO2 cell (max 0.46 mg g-1 s-1 to the total mass of active materials and 0.30 mg g-1 s-1 to the total mass of electrodes) was nearly 1 order of magnitude higher than those in most previous CDI studies, and this fast and efficient desalination performance was stabilized over 50 cycles.

Electrochemical Oxidation of Phenolic Compounds at Boron-Doped Diamond Anodes: Structure-Reactivity Relationships.

Electrochemical oxidation of phenolic compounds using boron-doped diamond (BDD) anodes has been shown as an effective approach to remove these contaminants from water. However, the understanding of the reaction mechanisms of substituted phenolic compounds at the BDD anode remains incomplete. In the present work, we investigated the electrochemical oxidation of 12 representative phenolic compounds (with varied substitution groups (e.g., -CH3, -OCH3, -NH2, -Cl, -OH, -COOH, -NO2, -CHO) and positions (-ortho, -meta, and -para)) at the BDD anode. Our analysis shows that unlike previous studies the two parameters, the Hammett constants of the substituents and the highest atomic charge on the aromatic ring, fail to adequately describe the reaction rate change when the chemical structures become complicated (i.e., with increased steric effects). Instead, a quantitative structure-property relationship (QSPR) was established with 26 molecular descriptors and using a partial least-squares regression approach. The QSPR analysis shows that the energy gap between the lowest unoccupied molecular orbital and the highest occupied molecular orbital, ELUMO - EHOMO, which reflects the chemical stability of a molecule, is the predominant molecular descriptor determining the reaction rate constant. Furthermore, the predicated rate constants agree well with the observed ones. The findings are consistent with previous studies of SnO2 anodes, suggesting that chemical structural parameters such as the molecular orbital energies are critical to consider when elucidating and predicating the electrochemical reactivity of phenolic compounds at these nonactive anodes.

Cross-section analysis of coal workers' pneumoconiosis and higher brachial-ankle pulse wave velocity within Kailuan study.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) is an independent predictor of cardiovascular events and mortality. However, there is no related data on the association of baPWVwith coal workers' pneumoconiosis (CWP). We explored the baPWV in subjects withCWP and the associated risk factors. METHODS: Thiscase-control study included 1,007 male CWP cases without a history of stroke and coronary heart disease and 1,007 matched controls from the Kailuan cohort study. All of the participants underwent assessment for baPWV and traditional cardiovascular risk factors. The cumulative silica dust exposure (work history linked to a job-exposure matrix) was estimated for the CWP cases. RESULTS: Compared with the controls, the CWP cases had higher baPWV (1762.0 ± 355 cm/s vs. 1718.6 ± 354 cm/s, P = 0.006) and a higher risk of increased baPWV (defined as more than the median baPWV of the population distribution; odds ratio 1.43, 95% confidence interval 1.11-1.83) after adjusting for traditional cardiovascular risk factors. Age ≥60 years, body mass index, heart rate, and hypertension were all significantly associated with increased baPWV in the CWP cases. Compared to non-CWP subjects without hypertension, the odds ratios for increased baPWV gradually increased (P for trend, 0.001) across the CWP subjects without hypertension (odds ratio 1.20, 95%confidence interval 0.90-1.61), subjects with hypertension alone (odds ratio 2.54, 95% confidence interval 1.95-3.30), and CWP subjects with hypertension (odds ratio 3.34, 95% confidence interval 2.56-4.37). We detected a significant positive exposure-response relationship between silica dust-exposure quartiles and increased baPWV in CWP cases (P for trend < 0.001). CONCLUSIONS: For patients with CWP, increased baPWV was associated with traditional cardiovascular risk factors and long-term silica dust exposure.

Alamethicin suppresses methanogenesis and promotes acetogenesis in bioelectrochemical systems.

Microbial electrosynthesis (MES) systems with mixed cultures often generate a variety of gaseous and soluble chemicals. Methane is the primary end product in mixed-culture MES because it is the thermodynamically most favorable reduction product of CO2. Here, we show that the peptaibol alamethicin selectively suppressed the growth of methanogens in mixed-culture MES systems, resulting in a shift of the solution and cathode communities to an acetate-producing system dominated by Sporomusa, a known acetogenic genus in MES systems. Archaea in the methane-producing control were dominated by Methanobrevibacter species, but no Archaea were detected in the alamethicin-treated reactors. No methane was detected in the mixed-culture reactors treated with alamethicin over 10 cycles (∼ 3 days each). Instead, acetate was produced at an average rate of 115 nmol ml(-1) day(-1), similar to the rate reported previously for pure cultures of Sporomusa ovata on biocathodes. Mixed-culture control reactors without alamethicin generated methane at nearly 100% coulombic recovery, and no acetate was detected. These results show that alamethicin is effective for the suppression of methanogen growth in MES systems and that its use enables the production of industrially relevant organic compounds by the inhibition of methanogenesis.

Energy recovery from solutions with different salinities based on swelling and shrinking of hydrogels.

Several technologies, including pressure-retarded osmosis (PRO), reverse electrodialysis (RED), and capacitive mixing (CapMix), are being developed to recover energy from salinity gradients. Here, we present a new approach to capture salinity gradient energy based on the expansion and contraction properties of poly(acrylic acid) hydrogels. These materials swell in fresh water and shrink in salt water, and thus the expansion can be used to capture energy through mechanical processes. In tests with 0.36 g of hydrogel particles 300 to 600 µm in diameter, 124 mJ of energy was recovered in 1 h (salinity ratio of 100, external load of 210 g, water flow rate of 1 mL/min). Although these energy recovery rates were relatively lower than those typically obtained using PRO, RED, or CapMix, the costs of hydrogels are much lower than those of membranes used in PRO and RED. In addition, fouling might be more easily controlled as the particles can be easily removed from the reactor for cleaning. Further development of the technology and testing of a wider range of conditions should lead to improved energy recoveries and performance.

Microbial community composition is unaffected by anode potential.

There is great controversy on how different set anode potentials affect the performance of a bioelectrochemical system (BES). It is often reported that more positive potentials improve acclimation and performance of exoelectrogenic biofilms, and alter microbial community structure, while in other studies relatively more negative potentials were needed to achieve higher current densities. To address this issue, the biomass, electroactivity, and community structure of anodic biofilms were examined over a wide range of set anode potentials (-0.25, -0.09, 0.21, 0.51, and 0.81 V vs a standard hydrogen electrode, SHE) in single-chamber microbial electrolysis cells. Maximum currents produced using a wastewater inoculum increased with anode potentials in the range of -0.25 to 0.21 V, but decreased at 0.51 and 0.81 V. The maximum currents were positively correlated with increasing biofilm biomass. Pyrosequencing indicated biofilm communities were all similar and dominated by bacteria most similar to Geobacter sulfurreducens. Differences in anode performance with various set potentials suggest that the exoelectrogenic communities self-regulate their exocellular electron transfer pathways to adapt to different anode potentials.

Comparison of hydrogen production and electrical power generation for energy capture in closed-loop ammonium bicarbonate reverse electrodialysis systems.

Currently, there is an enormous amount of energy available from salinity gradients, which could be used for clean hydrogen production. Through the use of a favorable oxygen reduction reaction (ORR) cathode, the projected electrical energy generated by a single pass ammonium bicarbonate reverse electrodialysis (RED) system approached 78 W h m(-3). However, if RED is operated with the less favorable (higher overpotential) hydrogen evolution electrode and hydrogen gas is harvested, the energy recovered increases by as much ~1.5× to 118 W h m(-3). Indirect hydrogen production through coupling an RED stack with an external electrolysis system was only projected to achieve 35 W h m(-3) or ~1/3 of that produced through direct hydrogen generation.

Encapsulate Co3O4 within ultrathin graphene sheets to enhance peroxymonosulfate activation by tuning surface electronic structures.

Heterojunctions composed of cobalt-based materials and carbon materials have been recognized as the efficient catalysts for peroxymonosulfate (PMS) activation to generate reactive oxygen species for the removal of environmental contaminants. However, the role of carbon materials in promoting the heterojunction systems has not been fully understood. This study synthesized a heterojunction material of graphene sheets encapsulating Co3O4 (GCO-500) through the pyrolysis of cobalt MOF and applied it to activate PMS for the removal of lomefloxacin. The results showed a high removal rate of 93.59 % with a degradation rate of k1 = 0.0156 min-1. Co3O4 clusters was encapsulated within ultrathin graphene sheets (<2 nm). DFT calculations revealed that graphene layers improve the electron transfer ability of Co3O4 and increased the d-band center of Co3O4 (-1.61 eV) that promote the adsorption of PMS on GCO-500 (-1.32 eV). In the meanwhile, organic pollutant was enriched in graphene layers with high adsorption energy (-13.08 eV), which greatly enhanced the degradation efficiency of pharmaceuticals. This study provides an effective catalyst for PMS activation and sheds light on the fundamental electronic-level understanding of cobalt-based and carbon heterojunction catalysts in PMS activation.

The Use of Digital PCR for the Diagnosis of Demodex Blepharitis.

PURPOSE: This was a pilot study to evaluate the efficacy of digital polymerase chain reaction detection of Demodex in eyelid margin swabs for the diagnosis of Demodex blepharitis. This study aims to explore the possibility of digital polymerase chain reaction detection to improve the diagnostic accuracy of Demodex blepharitis detection. METHODS: Volunteers were prospectively recruited and classified by experienced doctors into suspected Demodex blepharitis or healthy controls using slit-lamp evaluation of the eyelid margin and an inquiry about symptoms. Three eyelashes from each eyelid were epilated from participants in each group for microscopic observation and mite counting. Then, swabs from the eyelid margins of each eye were collected after the eyelashes were epilated and stored at -80 °C for future DNA extraction and digital polymerase chain reaction detection. The positive or negative results of both methods were compared for diagnostic accuracy, and the Kappa value was also calculated to evaluate their consistency. RESULTS: The accuracy of the digital polymerase chain reaction detection was 71.6% and that of the mite counting method was 75%. Their combined accuracy was improved to 77.3%. The Kappa value of the two methods was 0.505, indicating moderate consistency. CONCLUSION: Digital polymerase chain reaction detection of Demodex from ocular surface swabs was painless and noninvasive and is a potentially accurate quantitative method available for diagnosing Demodex blepharitis. This method is also complementary to the conventional mite counting method, particularly when a sufficient number of eyelashes cannot be effectively epilated.

Honokiol induces caspase-independent paraptosis via reactive oxygen species production that is accompanied by apoptosis in leukemia cells.

Our previous report has shown that honokiol (HNK), a constituent of Magnolia officinalis, induces a novel form of non-apoptotic programmed cell death in human leukemia NB4 and K562 cells. In this study, we further explored the relationship between the cell death pathway and cytoplasmic vacuolization and studied the underlying mechanism of leukemia cell death mediated by honokiol. The results showed that low concentrations of honokiol activated an novel alternative cell death fitted the criteria of paraptosis, such as cytoplasmic vacuolization derived from endoplasmic reticulum swelling, lack of caspase activation, and lack of apoptotic morphology. Results further indicated that the cell death was time- and concentration-dependent. In addition, honokiol-induced paraptosis did not involve membrane blebbing, chromatin condensation and phosphatidylserine exposure at the outer of the plasma membrane. The mechanism of the cell death may be associated, at least in part, with the increased generation of reactive oxygen species. Further analysis showed that honokiol induces cell death predominantly via paraptosis and to a certain extent via apoptosis in NB4 cells, and predominantly via apoptosis and to a certain extent via paraptosis in K562 cells. These observations suggest that cell death occurs via more than one pathway in leukemia cells and targeting paraptosis may be an alternative and promising avenue for honokiol in leukemia therapy.

An updated patent review of AKT inhibitors (2020 - present).

INTRODUCTION: Protein kinase B (Akt), an essential protein in the PI3K/Akt/mTOR signaling pathway, plays a crucial role in tumor progression. Over the past two years, different types of Akt modulators have continued to emerge in the patent literature. AREAS COVERED: This review focuses on the patent literature covering small molecule inhibitors, peptides, PROTACs, and antisense nucleic acids targetingAkt from 2020 to present. Also, we discuss the outcomes of several clinical trials, combination strategies for different mechanisms, and the application of Akt regulators in other non-oncology indications.Our search for relevant information was conducted using various databases, including the European Patent Office, SciFinder, andPubMed, from 01.2020 to 04.2023. EXPERT OPINION: In recent years, some combination therapeutic strategies involvingAkt inhibitors have shown promising clinical outcomes. Future research can be directed toward developing new applications of Akt inhibitors, which may have implications for other diseases beyond cancer. New attempts suggest that targeting allosteric sites may be a potential solution to the problem of isoform selectivity.Furthermore, directly knocking out Akt protein by using the degraderssuggests a promising direction for future development.

An overview of bioelectrokinetic and bioelectrochemical remediation of petroleum-contaminated soils.

The global problem of petroleum contamination in soils seriously threatens environmental safety and human health. Current studies have successfully demonstrated the feasibility of bioelectrokinetic and bioelectrochemical remediation of petroleum-contaminated soils due to their easy implementation, environmental benignity, and enhanced removal efficiency compared to bioremediation. This paper reviewed recent progress and development associated with bioelectrokinetic and bioelectrochemical remediation of petroleum-contaminated soils. The working principles, removal efficiencies, affecting factors, and constraints of the two technologies were thoroughly summarized and discussed. The potentials, challenges, and future perspectives were also deliberated to shed light on how to overcome the barriers and realize widespread implementation on large scales of these two technologies.

Endoplasmic reticulum stress and prion diseases.

The endoplasmic reticulum (ER), an important cellular organelle in eukaryotic cells, becomes dysfunctional following exposure to harmful stimuli. These stimuli can cause the ER stress response, which induces cell apoptosis due to changes in ER protein levels such as glucose-regulated protein. Current studies indicate that ER stress is closely related to the occurrence and development of neurodegenerative disorders, e.g., prion diseases. The pathogenic agent known as the misfolded prion protein may cause an imbalance in ER homeostasis and commit the neuron to a pathway of apoptosis; however, the specific mechanisms are still under intensive investigation. This review summarizes current research investigating the relationship between ER stress and prion diseases. These findings will aid in the development of novel strategies for diagnosis and therapies for prion and other neurodegenerative diseases.

A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment.

Peroxidasin (PXDN), also known as vascular peroxidase-1, is a newly discovered heme-containing peroxidase; it is involved in the formation of extracellular mesenchyme, and it catalyzes various substrate oxidation reactions in humans. However, the role and specific mechanism of PXDN in tumor are unclear, and no systematic pan-cancer studies on PXDN have been reported to date. This study employed data from multiple databases, including The Cancer Genome Atlas and The Genotype-Tissue Expression, to conduct a specific pan-cancer analysis of the effects of PXDN expression on cancer prognosis. Further, we evaluated the association of PXDN expression with DNA methylation status, tumor mutation burden, and microsatellite instability. Additionally, for the first time, the relationship of PXDN with the tumor microenvironment and infiltration of fibroblasts and different immune cells within different tumors was explored, and the possible molecular mechanism of the effect was also discussed. Our results provide a comprehensive understanding of the carcinogenicity of PXDN in different tumors and suggest that PXDN may be a potential target for tumor immunotherapy, providing a new candidate that could improve cancer clinical diagnosis and treatment.

Short-term effect of 0.01% atropine sulphate eye gel on myopia progression in children.

AIM: To investigate the effect of 0.01% atropine sulphate eye gel on myopia progression and axial elongation in a 6-month treatment in children. METHODS: Totally 185 children aged 6-12y with binocular myopia of 3.0 D or less in both eyes were enrolled in this prospective cohort study. The atropine group (n=125) received one drop of 0.01% atropine sulphate eye gel in each eye before bedtime daily. The control group included 60 matched children without drug intervention during the same period. The spherical equivalent and axial length was recorded at baseline and the sixth month of treatment. The efficacy was evaluated by the change of the spherical equivalent and axial length. Adverse events were also recorded. RESULTS: The average spherical equivalent and axial length at baseline were not statistically significant between the atropine group (-1.64±0.80 D, 24.13±0.76 mm) and the control group (-1.59±0.94 D, 24.06±0.77 mm, P>0.05). After 6mo, there was significantly difference in the spherical equivalent progression between the atropine and the control group (-0.27±0.33 vs -0.60±0.35 D, P<0.001), with a relative reduction of 55.0% in myopia progression. The increase in axial elongation in the atropine group was significantly less than control group (0.19±0.14 vs 0.26±0.14 mm, P<0.001), with a relative reduction of 26.9% in axial length. The 84.4% and 38.4% of the eyes progressed by less than 0.50 D and remained stable in the atropine group, compared with 51.7% and 4.2% in the control group. No adverse events were observed. CONCLUSION: Atropine sulphate eye gel 0.01% can slow down myopia progression and axial elongation in children with a 6-month treatment.

[Tear osmolarity and dry eye].

Dry eye is a common eye disease, and its incidence rate has been escalating. The increased tear osmolarity is one of the main reasons for complaint, damage and inflammation of dry eye patients. With the breakthrough of testing technology for tear osmolarity, more research and application of tear osmolarity was reported, and papers on tear osmolarity of normal eye and dry eye in different regions were also published. In this article, the progress of the tear osmolarity research, the range of tear osmolarity and its application in diagnosis and therapy of dry eye was introduced, and the prospect for the clinical application of hypotonic artificial tears was also discussed.

Facile Designed Manganese Oxide/Biochar for Efficient Salinity Gradient Energy Recovery in Concentration Flow Cells and Influences of Mono/Multivalent Ions.

Development of effective, environmentally friendly, facile large-scale processing, and low-cost materials is critical for renewable energy production. Here, MnOx/biochar composites were synthesized by a simple pyrolysis method and showed high performance for salinity gradient (SG) energy harvest in concentration flow cells (CFCs). The peak power density of CFCs with MnOx/biochar electrodes was up to 5.67 W m-2 (ave. = 0.91 W m-2) and stabilized for 500 cycles when using 1 and 30 g L-1 NaCl, which was attributed to their high specific capacitances and low electrode resistances. This power output was higher than all other reported MnO2 electrodes for SG energy harvest due to the synergistic effects between MnOx and biochar. When using a mixture with a molar fraction of 90% NaCl and 10% KCl (or Na2SO4, MgCl2, MgSO4, and CaCl2) in both feed solutions, the peak power density decreased by 2.3-40.1% compared to 100% NaCl solution with Ca2+ and Mg2+ showing the most pronounced negative effects. Our results demonstrated that the facile designed MnOx/biochar composite can be used for efficient SG energy recovery in CFCs with good stability, low cost, and less environmental impacts. When using natural waters as the feed solutions, pretreatment would be needed.