Charge Transfer Mechanism on a Cobalt-Polyoxometalate-TiO2 Photoanode for Water Oxidation in Acid.

We constructed a photoanode comprising the homogeneous water oxidation catalyst (WOC) Na8K8[Co9(H2O)6(OH)3(HPO4)2(PW9O34)3] (Co9POM) and nanoporous n-type TiO2 photoelectrodes (henceforth "TiO2-Co9POM") by first anchoring the cationic 3-aminopropyltrimethoxysilane (APS) ligand on a metal oxide light absorber, followed by treatment of the metal oxide-APS with a solution of the polyoxometalate WOC. The resulting TiO2-Co9POM photoelectrode exhibits a 3-fold oxygen evolution photocurrent enhancement compared to bare TiO2 in aqueous acidic conditions. Three-element (Co 2p, W 4f, and O 1s) X-ray photoelectron spectroscopy and Raman spectroscopy studies before and after use indicate that surface-bound Co9POM retains its structural integrity throughout all photoelectrochemical water oxidation studies reported here. Extensive charge-transfer mechanistic studies by photoelectrochemical techniques and transient absorption spectroscopy elucidate that Co9POM serves as an efficient WOC, extracting photogenerated holes from TiO2 on the picosecond time scale. This is the first comprehensive mechanistic investigation elucidating the roles of polyoxometalates in POM-photoelectrode hybrid oxygen evolution reaction systems.

Tailoring Interfaces for Enhanced Methanol Production from Photoelectrochemical CO2 Reduction.

Efficient and stable photoelectrochemical reduction of CO2 into highly reduced liquid fuels remains a formidable challenge, which requires an innovative semiconductor/catalyst interface to tackle. In this study, we introduce a strategy involving the fabrication of a silicon micropillar array structure coated with a superhydrophobic fluorinated carbon layer for the photoelectrochemical conversion of CO2 into methanol. The pillars increase the electrode surface area, improve catalyst loading and adhesion without compromising light absorption, and help confine gaseous intermediates near the catalyst surface. The superhydrophobic coating passivates parasitic side reactions and further enhances local accumulation of reaction intermediates. Upon one-electron reduction of the molecular catalyst, the semiconductor-catalyst interface changes from adaptive to buried junctions, providing a sufficient thermodynamic driving force for CO2 reduction. These structures together create a unique microenvironment for effective reduction of CO2 to methanol, leading to a remarkable Faradaic efficiency reaching 20% together with a partial current density of 3.4 mA cm-2, surpassing the previous record based on planar silicon photoelectrodes by a notable factor of 17. This work demonstrates a new pathway for enhancing photoelectrocatalytic CO2 reduction through meticulous interface and microenvironment tailoring and sets a benchmark for both Faradaic efficiency and current density in solar liquid fuel production.

Ultralow thermal conductivity of 2D Dion-Jacobson (PDA)(FA)n - 1PbnI3n + 1 perovskite films.

Two-dimensional (2D) perovskites exhibit enhanced thermal stability compared to three-dimensional perovskites, especially the emerging 2D Dion-Jacobson (DJ) phase perovskite. However, the heat transfer mechanisms in DJ phase perovskites are rarely reported. Herein, we determine thermal conductivities of (PDA)(FA)n - 1PbnI3n + 1 films with n = 1-6 by time-domain thermoreflectance. The measured results indicate that the thermal conductivities of these films are extremely low, showing a trend from decline to rise with increasing n values, and reaching to the lowest when n = 2. We measure the propagation of acoustic phonons in films with n = 1-3 by time-domain Brillouin scattering and find phonon velocity plays a key role in the thermal conductivity, which can be explained by the mismatch of spring constants between the inorganic layer and the organic layer using the bead-spring model. The gradually increasing thermal conductivity for larger n values is attributed to the gradual transformation of the grain orientation from horizontal to vertical, which is demonstrated by the grazing-incidence wide-angle x ray scattering (GIWAXS) results. Our work deepens the understanding of the thermal transport process in 2D DJ phase perovskite films and provides insights into thermal management solutions for their devices.

A contactless in situ EFISH method for measuring electrostatic potential profile of semiconductor/electrolyte junctions.

In photoelectrochemical cells, promising devices for directly converting solar energy into storable chemical fuels, the spatial variation of the electrostatic potential across the semiconductor-electrolyte junction is the key parameter that determines the cell performance. In principle, electric field induced second harmonic generation (EFISH) provides a contactless in situ spectroscopic tool to measure the spatial variation of electrostatic potential. However, the total second harmonic generation (SHG) signal contains the contributions of the EFISH signals of semiconductor space charge layer and the electric double layer, in addition to the SHG signal of the electrode surface. The interference of these complex quantities hinders their analysis. In this work, to understand and deconvolute their contributions to the total SHG signals, bias-dependent SHG measurements are performed on the rutile TiO2(100)-electrolyte junction as a function of light polarization and crystal azimuthal angle (angle of the incident plane relative to the crystal [001] axis). A quadratic response between SHG intensity and the applied potential is observed in both the accumulation and depletion regions of TiO2. The relative phase difference and amplitude ratio are extracted at selected azimuthal angles and light polarizations. At 0° azimuthal angle and s-in-p-out polarization, the SHG intensity minimum has the best match with the TiO2 flatband potential due to the orthogonal relative phase difference between bias-dependent and bias-independent SHG terms. We further measure the pH-dependent flatband potential and probe the photovoltage under open circuit conditions using the EFISH technique, demonstrating the capability of this contactless method for measuring electrostatic potential at semiconductor-electrolyte junctions.

Patient Self-Management Scale After Total Knee Arthroplasty (PSMS-TKA): Instrument Development and Cross-Sectional Validation Study.

BACKGROUND: Effective self-management after total knee arthroplasty (TKA) not only improves patients' knee pain and physical function but also improves quality of life. However, there is no assessment tool that can be targeted to evaluate the self-management level of patients after TKA. This study aimed to develop and validate a scale to specifically assess the level of self-management in patients after TKA. METHODS: The study was conducted in 2 steps: (1) instrument development and (2) psychological tests (n = 428). For the instrument development portion, scale items were generated through a literature review and semi-structured interviews, then reviewed and revised by a panel of experts, and assessed for content validity and pilot testing. For the psychometric tests component, items were analyzed using corrected item-total scale correlations, the critical ratio method, and Cronbach's α. Construct validity was evaluated using exploratory factor analysis and validation factor analysis. Criterion correlation validity was checked by calculating Pearson's correlation coefficient using the Arthritis Self-Efficacy Scale-8 and the scale developed in this study. Internal consistency reliability was evaluated using Cronbach's α and fold-half reliability, and retest reliability was assessed using intragroup correlation coefficients. RESULTS: The Patient Self-Management Scale after Total Knee Arthroplasty (PSMS-TKA) comprises 4 factors and 23 items that assess daily behavior management, disease information management, psychosocial management, and exercise rehabilitation management. Exploratory factor analysis and validation factor analysis yielded a stable 4-factor model for the 23 items. The PSMS-TKA demonstrated good criterion-related validity when using the Arthritis Self-Efficacy-8 as a criterion. The Cronbach's α of the PSMS-TKA was 0.903, the split-half reliability was 0.934, and the test-retest reliability correlation coefficient was 0.887 (P < .01); thus, the reliability of the scale is good. CONCLUSIONS: The PSMS-TKA developed in this study has good validity and reliability and can be used to assess the level of self-management in patients after TKA. The scale helps healthcare professionals understand the level of self-management of patients undergoing TKA.

Direct Vibrational Stark Shift Probe of Quasi-Fermi Level Alignment in Metal Nanoparticle Catalyst-Based Metal-Insulator-Semiconductor Junction Photoelectrodes.

Photoelectrodes consisting of metal-insulator-semiconductor (MIS) junctions are a promising candidate architecture for water splitting and for the CO2 reduction reaction (CO2RR). The photovoltage is an essential indicator of the driving force that a photoelectrode can provide for surface catalytic reactions. However, for MIS photoelectrodes that contain metal nanoparticles, direct photovoltage measurements at the metal sites under operational conditions remain challenging. Herein, we report a new in situ spectroscopic approach to probe the quasi-Fermi level of metal catalyst sites in heterogeneous MIS photoelectrodes via surface-enhanced Raman spectroscopy. Using a CO2RR photocathode, nanoporous p-type Si modified with Ag nanoparticles, as a prototype, we demonstrate a selective probe of the photovoltage of ∼0.59 V generated at the Si/SiOx/Ag junctions. Because it can directly probe the photovoltage of MIS heterogeneous junctions, this vibrational Stark probing approach paves the way for the thermodynamic evaluation of MIS photoelectrodes with varied architectural designs.

Direct In Situ Measurement of Quantum Efficiencies of Charge Separation and Proton Reduction at TiO2-Protected GaP Photocathodes.

Photoelectrochemical solar fuel generation at the semiconductor/liquid interface consists of multiple elementary steps, including charge separation, recombination, and catalytic reactions. While the overall incident light-to-current conversion efficiency (IPCE) can be readily measured, identifying the microscopic efficiency loss processes remains difficult. Here, we report simultaneous in situ transient photocurrent and transient reflectance spectroscopy (TRS) measurements of titanium dioxide-protected gallium phosphide photocathodes for water reduction in photoelectrochemical cells. Transient reflectance spectroscopy enables the direct probe of the separated charge carriers responsible for water reduction to follow their kinetics. Comparison with transient photocurrent measurement allows the direct probe of the initial charge separation quantum efficiency (ϕCS) and provides support for a transient photocurrent model that divides IPCE into the product of quantum efficiencies of light absorption (ϕabs), charge separation (ϕCS), and photoreduction (ϕred), i.e., IPCE = ϕabsϕCSϕred. Our study shows that there are two general key loss pathways: recombination within the bulk GaP that reduces ϕCS and interfacial recombination at the junction that decreases ϕred. Although both loss pathways can be reduced at a more negative applied bias, for GaP/TiO2, the initial charge separation loss is the key efficiency limiting factor. Our combined transient reflectance and photocurrent study provides a time-resolved view of microscopic steps involved in the overall light-to-current conversion process and provides detailed insights into the main loss pathways of the photoelectrochemical system.

Homoleptic Al(III) Photosensitizers for Durable CO2 Photoreduction.

Exploiting noble-metal-free systems for high-performance photocatalytic CO2 reduction still presents a key challenge, partially due to the long-standing difficulties in developing potent and durable earth-abundant photosensitizers. Therefore, based on the very cheap aluminum metal, we have deployed a systematic series of homoleptic Al(III) photosensitizers featuring 2-pyridylpyrrolide ligands for CO2 photoreduction. The combined studies of steady-state and time-resolved spectroscopy as well as quantum chemical calculations demonstrate that in anerobic CH3CN solutions at room temperature, visible-light excitation of the Al(III) photosensitizers leads to an efficient population of singlet excited states with nanosecond-scale lifetimes and notable emission quantum yields (10-40%). The results of transient absorption spectroscopy further identified the presence of emissive singlet and unexpectedly nonemissive triplet excited states. More importantly, the introduction of methyl groups at the pyrrolide rings can greatly improve the visible-light absorption, reducing power, and durability of the Al(III) photosensitizers. With triethanolamine, BIH (1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole), and an Fe(II)-quaterpyridine catalyst, the most methylated Al(III) photosensitizer achieves an apparent quantum efficiency of 2.8% at 450 nm for selective (>99%) CO2-to-CO conversion, which is nearly 28 times that of the unmethylated one (0.1%) under identical conditions. The optimal system realizes a maximum turnover number of 10250 and higher robustness than the systems with Ru(II) and Cu(I) benchmark photosensitizers. Quenching experiments using fluorescence spectroscopy elucidate that the photoinduced electron transfer in the Al(III)-sensitized system follows a reductive quenching pathway. The remarkable tunability and cost efficiency of these Al(III) photosensitizers should allow them as promising components in noble-metal-free systems for solar fuel conversion.

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity.

Ellagic acid (EA) is present at relatively high concentrations in many berries and has many beneficial health effects, including anticancer properties. To improve the development and utilization of blackberry fruit nutrients, we divided Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW. Single-factor tests and response surface methodology were used to optimize the extraction process, while macroporous resin adsorption and alkali dissolution, acid precipitation, and solvent recrystallization were used for purification. The highest purity of the final EA powder was 90%. The anticancer assessment results determined by MTT assay showed that EA inhibited HeLa cells with an IC50 of 35 µg/mL, and the apoptosis rate of the cells increased in a dose-dependent manner, with the highest rate of about 67%. We evaluated the changes in the mRNA levels of genes related to the EA-mediated inhibition of cancer cell growth and initially verified the PI3K/PTEN/AKT/mTOR pathway as the pathway by which EA inhibits HeLa cell growth. We hope to provide a theoretical basis for the deep exploration and utilization of this functional food.

Proteins from Blackberry Seeds: Extraction, Osborne Isolate, Characteristics, Functional Properties, and Bioactivities.

Blackberry fruit contains high levels of nutrients and phenolic compounds. Blackberry pomace accounts for 20~30% of its whole fruit during processing and is generally treated as fertilizer. Blackberry pomace has many seeds that contain carbohydrates, polyphenols, flavonoids, pectin, protein, and other bioactive nutrients. However, its functional properties and seed protein compositions have not been reported. We used a single-factor experiment, response surface, and Osborne isolate method to extract protein isolate, albumin, globulin, glutelin, and prolamin from blackberry seeds for the first time and evaluated their characteristics and functional properties. Glutelin and protein isolate showed good water-holding capacity, emulsification, and foaming capacity, while albumin and globulin showed good oil-holding capacity and thermal stability. They were found to have good antioxidant activities that might be good DPPH free radical scavengers, especially prolamin, which has the lowest IC50 value (15.76 µg/mL). Moreover, globulin had the lowest IC50 value of 5.03 µg/mL against Hela cells, 31.82 µg/mL against HepG2 cells, and 77.81 µg/mL against MCF-7 cells and a high selectivity index (SI), which suggested globulin had better anti-cervical, antihepatoma, and anti-breast activity but relatively low cytotoxicity. These seed proteins may have great prospects for the development and application of food and drugs in the future.

The Extraction and High Antiproliferative Effect of Anthocyanin from Gardenblue Blueberry.

Blueberries are rich in flavonoids, anthocyanins, phenolic acids, and other bioactive substances. Anthocyanins are important functional components in blueberries. We collected 65 varieties of blueberries to investigate their nutritional and functional values. Among them, Gardenblue had the highest anthocyanin content, with 2.59 mg/g in fresh fruit. After ultrasound-assisted solvent extraction and macroporous resin absorption, the content was increased to 459.81 mg/g in the dried powder. Biological experiments showed that Gardenblue anthocyanins (L1) had antiproliferative effect on cervical cancer cells (Hela, 51.98 µg/mL), liver cancer cells (HepG2, 23.57 µg/mL), breast cancer cells (MCF-7, 113.39 µg/mL), and lung cancer cells (A549, 76.10 µg/mL), and no apparent toxic effects were indicated by methyl thiazolyl tetrazolium (MTT) assay, especially against HepG2 cells both in vitro and in vivo. After combining it with DDP (cisplatin) and DOX (doxorubicin), the antiproliferative effects were enhanced, especially when combined with DOX against HepG2 cells; the IC50 value was 0.02 µg/mL. This was further evidence that L1 could inhibit cell proliferation by inducing apoptosis. The detailed mechanism might be L1 interacting with DNA in an intercalation mode that changes or destroys DNA, causing apoptosis and inhibiting cell proliferation. The findings of this study suggest that L1 extract can be used as a functional agent against hepatoma carcinoma cells.

Synergizing Electron and Heat Flows in Photocatalyst for Direct Conversion of Captured CO2.

We report a ternary hybrid photocatalyst architecture with tailored interfaces that boost the utilization of solar energy for photochemical CO2 reduction by synergizing electron and heat flows in the photocatalyst. The photocatalyst comprises cobalt phthalocyanine (CoPc) molecules assembled on multiwalled carbon nanotubes (CNTs) that are decorated with nearly monodispersed cadmium sulfide quantum dots (CdS QDs). The CdS QDs absorb visible light and generate electron-hole pairs. The CNTs rapidly transfer the photogenerated electrons from CdS to CoPc. The CoPc molecules then selectively reduce CO2 to CO. The interfacial dynamics and catalytic behavior are clearly revealed by time-resolved and in situ vibrational spectroscopies. In addition to serving as electron highways, the black body property of the CNT component can create local photothermal heating to activate amine-captured CO2 , namely carbamates, for direct photochemical conversion without additional energy input.

Nanoscale TiO2 Protection Layer Enhances the Built-In Field and Charge Separation Performance of GaP Photoelectrodes.

Nanoscale oxide layer protected semiconductor photoelectrodes show enhanced stability and performance for solar fuels generation, although the mechanism for the performance enhancement remains unclear due to a lack of understanding of the microscopic interfacial field and its effects. Here, we directly probe the interfacial fields at p-GaP electrodes protected by n-TiO2 and its effect on charge carriers by transient reflectance spectroscopy. Increasing the TiO2 layer thickness from 0 to 35 nm increases the field in the GaP depletion region, enhancing the rate and efficiency of interfacial electron transfer from the GaP to TiO2 on the ps time scale as well as retarding interfacial recombination on the microsecond time scale. This study demonstrates a general method for providing a microscopic view of the photogenerated charge carrier's pathway and loss mechanisms from the bulk of the electrode to the long-lived separated charge at the interface that ultimately drives the photoelectrochemical reactions.

Lower normal free thyroxine is associated with a higher risk of metabolic syndrome: a retrospective cohort on Chinese population.

BACKGROUND: Recently, the relationship between thyroid hormones (THs) across the euthyroid ranges and metabolic syndrome (MetS) has been widely discussed. This study aimed to present specific cutoff values of THs to assess the association between THs and MetS in a euthyroid cohort. METHODS: Data of 2694 subjects, aged 18-80 years, who attended health examination in Xi'an Electric Power Central Hospital from April 2011 to December 2015 were collected and analyzed. The first cohort enrolled 929 participants (followed up by 2221 person-years totally) to assess correlations between serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) levels and MetS. The second cohort included 698 participants (followed up by 1709 person-years totally) to evaluate relationships between serum free triiodothyronine (FT3), free thyroxine (FT4) levels and MetS. MetS was defined according to the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) scientific statements of 2009. Euthyroidism was defined as serum TSH, FT3 and FT4 levels within the reference ranges without taking any thyroid medication. RESULTS: The cutoff values for TSH, T3, T4, FT3 and FT4 were 2.0mIU/L, 1.9 nmol/L, 117 nmol/L, 4.3 pmol/L and 16 pmol/L, respectively. Participants were categorized into two groups according to cutoff values: the lower-THs group and the higher-THs group. There was no significant difference in the risk of MetS between two groups in TSH, T3, T4 and FT3. The incidence of MetS was significantly higher in lower-FT4 group than higher-FT4 group (1.00 vs 0.622 (0.458, 0.846), P = 0.002). The lower-FT4/higher-TSH group had the highest hazard ratios of MetS. (2.131vs 1.0 (1.380,3.291), P = 0.006). CONCLUSIONS: Lower normal FT4 (FT4 ≤ 16.0 pmol/L) is an independent risk factor for MetS, and lower normal thyroid function (TSH > 2.0 mIU/L and FT4 ≤ 16.0 pmol/L) is associated with a higher risk of developing MetS.

The association between subclinical hypothyroidism and metabolic syndrome: an update meta-analysis of observational studies.

The association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) has been widely discussed. This study aimed to conduct an update and comprehensive meta-analysis to reveal the risk of MetS and its components in SCH. PubMed, Embase and ISI Web of Knowledge were searched to identify relevant studies through February 20th, 2020. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Both fixed-effects and random-effects models were used. In total, 18 articles (19 studies) incorporating 79,727 participants were included. The pooled OR for MetS comparing subjects with SCH with euthyroid subjects was 1.28 (95% CI: 1.19 to 1.39, p = 0.04, I2 = 40%). Subgroup analysis results showed significant associations of SCH and MetS in the adult subgroup (OR = 1.28, 95% CI: 1.18-1.40), Asian population subgroup (OR = 1.30, 95% CI: 1.19-1.42) and cross-sectional study design subgroup (OR = 1.31, 95% CI: 1.16-1.47). Significant associations of SCH and MetS also existed in all MetS definition criteria subgroups except the Chinese Diabetes Society (CDS) subgroup. SCH was correlated with MetS and was not affected by the subgroup analysis stratified by the proportion of females in the total population, the TSH cutoff value in SCH diagnostic criteria, or the adjustment for confounding factors. SCH was identified to be associated with an increased risk of obesity, hypertension, high triglyceride (TG) levels and low high-density lipoprotein cholesterol (HDL-C) levels. In conclusion, SCH is significantly associated with an increased risk of MetS and four out of five components of MetS.

Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo.

Several bioactive dehydroabietylamine Schiff-bases (L1-L4), amides (L5-L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). For HepG2 cells, L1, L2 and L3 had higher anti-HepG2 activity, especially L1 (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L1, L2, L3 and L4 had higher anti-MCF-7 activity, especially L3(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L2 and L3 had higher anti-A549 activity. Furthermore, L1 and L3 may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L1, L2 and L3 could induce apoptosis through intercalating into DNA.

Hyperglycemia-induced cardiomyocyte death is mediated by lysosomal membrane injury and aberrant expression of cathepsin D.

Hyperglycemia is an independent risk factor for diabetic heart failure. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Previous studies have shown an association between lysosomal dysfunction and diabetic heart injury. The present study examined if mimicking hyperglycemia in cultured cardiomyocytes could induce lysosomal membrane permeabilization (LMP), leading to the release of lysosome enzymes and subsequent cell death. High glucose (HG) reduced the number of lysosomes with acidic pH as shown by a fluorescent pH indicator. Also, HG induced lysosomal membrane injury as shown by an accumulation of Galectin3-RFP puncta, which was accompanied by the leakage of cathepsin D (CTSD), an aspartic protease that normally resides within the lysosomal lumen. Furthermore, CTSD expression was increased in HG-cultured cardiomyocytes and in the hearts of 2 mouse models of type 1 diabetes. Either CTSD knockdown with siRNA or inhibition of CTSD activity by pepstatin A markedly diminished HG-induced cardiomyocyte death, while CTSD overexpression exaggerated HG-induced cell death. Together, these results suggested that HG increased CTSD expression, induced LMP and triggered CTSD release from the lysosomes, which collectively contributed to HG-induced cardiomyocyte injury.

Enhanced mTOR complex 1 signaling attenuates diabetic cardiac injury in OVE26 mice.

The protein kinase mechanistic target of rapamycin (mTOR) performs diverse cellular functions through 2 distinct multiprotein complexes, mTOR complex (mTORC)1 and 2. Numerous studies using rapamycin, an mTORC1 inhibitor, have implicated a role for mTORC1 in several types of heart disease. People with diabetes are more susceptible to heart failure. mTORC1 activity is increased in the diabetic heart, but its functional significance remains controversial. To investigate the role of mTORC1 in the diabetic heart, we crossed OVE26 type 1 diabetic mice with transgenic mice expressing a constitutively active mTOR (mTORca) or kinase-dead mTOR (mTORkd) in the heart. The expression of mTORca or mTORkd affected only mTORC1 but not mTORC2 activities, with corresponding changes in the activities of autophagy, a cellular degradation pathway negatively regulated by mTORC1. Diabetic cardiac damage in OVE26 mice was dramatically reduced by mTORca but exacerbated by mTORkd expression as assessed by changes in cardiac function, oxidative stress, and myocyte apoptosis. These findings demonstrated that the enhanced mTORC1 signaling in the OVE26 diabetic heart was an adaptive response that limited cardiac dysfunction, suggesting that manipulations that enhance mTORC1 activity may reduce diabetic cardiac injury, in sharp contrast to the results previously obtained with rapamycin.-Xu, X., Kobayashi, S., Timm, D., Huang, Y., Zhao, F., Shou, W., Liang, Q. Enhanced mTOR complex 1 signaling attenuates diabetic cardiac injury in OVE26 mice.

Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy.

Doxorubicin (Dox) is a widely used antineoplastic agent that can cause heart failure. Dox cardiotoxicity is closely associated with mitochondrial damage. Mitochondrial fission and mitophagy are quality control mechanisms that normally help maintain a pool of healthy mitochondria. However, unchecked mitochondrial fission and mitophagy may compromise the viability of cardiomyocytes, predisposing them to cell death. Here, we tested this possibility by using Dox-treated H9c2 cardiac myoblast cells expressing either the mitochondria-targeted fluorescent protein MitoDsRed or the novel dual-fluorescent mitophagy reporter mt-Rosella. Dox induced mitochondrial fragmentation as shown by reduced form factor, aspect ratio, and mean mitochondrial size. This effect was abolished by short interference RNA-mediated knockdown of dynamin-related protein 1 (DRP1), a major regulator of fission. Importantly, DRP1 knockdown decreased cell death as indicated by the reduced number of propidium iodide-positive cells and the cleavage of caspase-3 and poly (ADP-ribose) polymerase. Moreover, DRP1-deficient mice were protected from Dox-induced cardiac damage, strongly supporting a role for DRP1-dependent mitochondrial fragmentation in Dox cardiotoxicity. In addition, Dox accelerated mitophagy flux, which was attenuated by DRP1 knockdown, as assessed by the mitophagy reporter mt-Rosella, suggesting the necessity of mitochondrial fragmentation in Dox-induced mitophagy. Knockdown of parkin, a positive regulator of mitophagy, dramatically diminished Dox-induced cell death, whereas overexpression of parkin had the opposite effect. Together, these results suggested that Dox cardiotoxicity was mediated, at least in part, by the increased mitochondrial fragmentation and accelerated mitochondrial degradation by the lysosome. Strategies that limit mitochondrial fission and mitophagy in the physiologic range may help reduce Dox cardiotoxicity.-Catanzaro, M. P., Weiner, A., Kaminaris, A., Li, C., Cai, F., Zhao, F., Kobayashi, S., Kobayashi, T., Huang, Y., Sesaki, H., Liang, Q. Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy.

The proportion of peripheral blood Tregs among the CD4+ T cells of autoimmune thyroid disease patients: a meta-analysis.

Autoimmune thyroid disease (AITD) is characterized by a loss of self-tolerance to thyroid antigen. Tregs, whose proportions are controversial among CD4+ T cell from AITD patients (AITDs), are crucial in immune tolerance. Considering that drugs might affect Treg levels, we assumed that the differences originated from different treatment statuses. Thus, we performed a meta-analysis to explore proportions of Tregs in untreated and treated AITDs. PubMed, Embase and ISI Web of Knowledge were searched for relevant studies. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Subgroup analysis based on different diseases and cell surface markers was performed. Egger linear regression analysis was used to assess publication bias. Approximately 1,100 AITDs and healthy controls (HCs) from fourteen studies were included. Proportions of Tregs among CD4+ T cells of untreated AITDs were significantly lower than those in HCs (p = 0.002), but were not in treated patients (p = 0.40). Subgroup analysis revealed lower proportions of Tregs in untreated Graves' disease patients (GDs) (p = 0.001) but did not show obvious differences in untreated Hashimoto's thyroiditis patients (HTs) (p = 0.62). Furthermore, proportions of circulating FoxP3+ Tregs were reduced in untreated GDs (p < 0.00001) and HTs (p = 0.04). No publication bias was found. In this first meta-analysis exploring proportions of circulating Tregs among CD4+ T cells of AITDs with different treatment statuses, we found that Tregs potentially contribute to the pathogenesis of AITD but function differently in GD and HT. Remarkably, FoxP3+ Tregs, which were decreased in both diseases, might be promising targets for novel therapies.