Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches.

Anticytotoxic T lymphocyte-associated protein 4 (CTLA4) antibodies have shown potent antitumor activity, but systemic immune activation leads to severe immune-related adverse events, limiting clinical usage. We developed novel, conditionally active biologic (CAB) anti-CTLA4 antibodies that are active only in the acidic tumor microenvironment. In healthy tissue, this binding is reversibly inhibited by a novel mechanism using physiological chemicals as protein-associated chemical switches (PaCS). No enzymes or potentially immunogenic covalent modifications to the antibody are required for activation in the tumor. The novel anti-CTLA4 antibodies show similar efficacy in animal models compared to an analog of a marketed anti-CTLA4 biologic, but have markedly reduced toxicity in nonhuman primates (in combination with an anti-PD1 checkpoint inhibitor), indicating a widened therapeutic index (TI). The PaCS encompass mechanisms that are applicable to a wide array of antibody formats (e.g., ADC, bispecifics) and antigens. Examples shown here include antibodies to EpCAM, Her2, Nectin4, CD73, and CD3. Existing antibodies can be engineered readily to be made sensitive to PaCS, and the inhibitory activity can be optimized for each antigen's varying expression level and tissue distribution. PaCS can modulate diverse physiological molecular interactions and are applicable to various pathologic conditions, enabling differential CAB antibody activities in normal versus disease microenvironments.

Using 3.0 eV Large Bandgap Conjugated Polymer as Host Donor to Construct Ternary Semi-Transparent Polymer Solar Cells: Increased Average Visible Transmittance and Modified Color Temperature.

Although optical engineering strategy has been utilized to optimize average visible transmittance (AVT) of semi-transparent organic solar cells (ST-OSCs), judicious selection of active layer materials should be more direct and basic. Herein, an efficient ternary active layer is constructed with a wide bandgap (3.0 eV) fluorescent polymer FC-S1 as host donor, a middle bandgap polymer PM6 as guest donor, and a narrow bandgap non-fullerene Y6-BO as acceptor. Using FC-S1 as the host donor can allow more visible photons to penetrate the device. In the absence of optical engineering, the ternary ST-OSC with FC-S1:PM6:Y6-BO = 1:0.3:1.5 active layer of 30 nm thickness displays a much higher AVT of 49.28% than that of 32.34% for a PM6:Y6-BO = 1.3:1.5 based binary ST-OSC. The ternary ST-OSC provides a good power conversion efficiency of 6.01%, only slightly lower than 7.15% for the binary ST-OSC. The ternary ST-OSC also demonstrates a color rendering index (CRI) of 87 and a correlated color temperature (CCT) of 6916 K, all better than CRI of 80 and CCT of 9022 K for the binary ST-OSC. Moreover, the backbone of FC-S1 is mainly composed by fluorene and carbazole, two easily-accessible aromatic rings, which would meet low-cost concern of ST-OSCs.

Dietary fibers fractionated from gardenia (Gardenia jasminoides Ellis) husk: structure and in vitro hypoglycemic effect.

BACKGROUND: Gardenia (Gardenia jasminoides Ellis) husk rich in dietary fiber is a byproduct of fructus processing, and commonly discarded as waste. The husk was fractionated by sequential extraction into four fractions: water-soluble fiber (W-SF), acid-soluble fiber (Ac-SF), alkali-soluble fiber (Al-SF) and insoluble residue fiber (IRF). The aim of this study was to investigate the differences in structure and in vitro hypoglycemic effect of these fibers. RESULTS: Monosaccharide composition and Fourier transform infrared spectra showed that the major component might be pectin for W-SF and Ac-SF, xylan as well as pectin for Al-SF and cellulose for IRF. These fibers offered excellent water-holding capacity and swelling capacity, except that IRF was only slightly swellable in water. W-SF exhibited significantly higher capacities to adsorb glucose (2.408 mmol g-1 at a glucose concentration of 200 mmol L-1 ) and inhibit α-amylase activity (29.48-49.45% inhibition rate at a concentration of 4-8 mg mL-1 ), probably caused by the higher viscosity and hydration properties; while Ac-SF, Al-SF and IRF (especially Al-SF) were more effective in retarding the glucose diffusion across a dialysis membrane (34.97-41.67% at 20-30 min), which might be attributed to particle size and specific surface area. All the fibers could quench the intrinsic fluorescence of α-amylase to some degree. CONCLUSIONS: Dietary fiber from gardenia husk, especially W-SF, can be used as a potential hypoglycemic ingredient in diabetic functional foods. © 2020 Society of Chemical Industry.

Distinct mechanisms govern the phosphorylation of different SR protein splicing factors.

Serine-arginine (SR) proteins are essential splicing factors containing a canonical RNA recognition motif (RRM), sometimes followed by a pseudo-RRM, and a C-terminal arginine/serine-rich (RS) domain that undergoes multisite phosphorylation. Phosphorylation regulates the localization and activity of SR proteins, and thus may provide insight into their differential biological roles. The phosphorylation mechanism of the prototypic SRSF1 by serine-arginine protein kinase 1 (SRPK1) has been well-studied, but little is known about the phosphorylation of other SR protein members. In the present study, interaction and kinetic assays unveiled how SRSF1 and the single RRM-containing SRSF3 are phosphorylated by SRPK2, another member of the SRPK family. We showed that a conserved SRPK-specific substrate-docking groove in SRPK2 impacts the binding and phosphorylation of both SR proteins, and the localization of SRSF3. We identified a nonconserved residue within the groove that affects the kinase processivity. We demonstrated that, in contrast to SRSF1, for which SRPK-mediated phosphorylation is confined to the N-terminal region of the RS domain, SRSF3 phosphorylation sites are spread throughout its entire RS domain in vitro Despite this, SRSF3 appears to be hypophosphorylated in cells at steady state. Our results suggest that the absence of a pseudo-RRM renders the single RRM-containing SRSF3 more susceptible to dephosphorylation by phosphatase. These findings suggest that the single RRM- and two RRM-containing SR proteins represent two subclasses of phosphoproteins in which phosphorylation statuses are maintained by unique mechanisms, and pose new directions to explore the distinct roles of SR proteins in vivo.

A peptidylic inhibitor for neutralizing expanded CAG RNA-induced nucleolar stress in polyglutamine diseases.

Polyglutamine (polyQ) diseases are a class of progressive neurodegenerative disorders characterized by the expression of both expanded CAG RNA and misfolded polyQ protein. We previously reported that the direct interaction between expanded CAG RNA and nucleolar protein nucleolin (NCL) impedes preribosomal RNA (pre-rRNA) transcription, and eventually triggers nucleolar stress-induced apoptosis in polyQ diseases. Here, we report that a 21-amino acid peptide, named "beta-structured inhibitor for neurodegenerative diseases" (BIND), effectively suppresses toxicity induced by expanded CAG RNA. When administered to a cell model, BIND potently inhibited cell death induced by expanded CAG RNA with an IC50 value of ∼0.7 µM. We showed that the function of BIND is dependent on Glu2, Lys13, Gly14, Ile18, Glu19, and Phe20. BIND treatment restored the subcellular localization of nucleolar marker protein and the expression level of pre-45s rRNA Through isothermal titration calorimetry analysis, we demonstrated that BIND suppresses nucleolar stress via a direct interaction with CAG RNA in a length-dependent manner. The mean binding constants (KD) of BIND to SCA2CAG22 , SCA2CAG42 , SCA2CAG55 , and SCA2CAG72 RNA are 17.28, 5.60, 4.83, and 0.66 µM, respectively. In vivo, BIND ameliorates retinal degeneration and climbing defects, and extends the lifespan of Drosophila expressing expanded CAG RNA. These effects suggested that BIND can suppress neurodegeneration in diverse polyQ disease models in vivo and in vitro without exerting observable cytotoxic effect. Our results collectively demonstrated that BIND is an effective inhibitor of expanded CAG RNA-induced toxicity in polyQ diseases.

Theoretical Design of D-π-A-A Sensitizers with Narrow Band Gap and Broad Spectral Response Based on Boron Dipyrromethene for Dye-Sensitized Solar Cells.

Dye-sensitized solar cells based on boron dipyrromethene (BODIPY) have gained widespread attention in recent years because of their easy structural modification, strong light absorption, and photostability. In this paper, a series of dyes with single or double acceptors based on the BODIPY framework have been designed and compared by density functional theory calculation. Results show that the dyes with double acceptors exhibit smaller band gap and broader red-shift absorption peaks than their counterparts with single acceptors. To further improve the dye performance, polythiophenes and electron donating groups are successively introduced into BODIPY and donor moieties of double-acceptor dyes. The introduction of polythiophene effectively improved the light harvesting efficiency (LHE) from 0.79 to 0.96. And, the stronger electron donating groups create a narrow band gap, resulting in a broad absorption band in the range of 400-1600 nm. These modifications not only broaden the absorption range but also facilitate electron injection, thereby improving the photoelectric conversion efficiency, which is beneficial for the potential application of BODIPY sensitizers in the field of photovoltaics.

Increased Ratio of Circulating T-Helper 1 to T-Helper 2 Cells and Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction: A Prospective Observational Study.

BACKGROUND This study aimed to determine the association between CD4-positive T-helper (Th) cell subsets, T-helper 1 (Th1) and T-helper 2 (Th2) in patients with acute myocardial infarction (AMI) and the severity of coronary artery disease (CAD) determined by coronary artery angiography. MATERIAL AND METHODS Three groups of patients with AMI who underwent coronary angiography and percutaneous coronary intervention (PCI) included patients with stable CAD (n=35), ST-segment elevation myocardial infarction (STEMI) (n=30), and non-STEMI (NSTEMI) (n=35), and controls (n=33). Measurement of high-sensitivity cardiac troponin T (hs-cTnT) was performed. The numbers of circulating CD4-positive Th1 and Th2 cells were measured using flow cytometry. Plasma levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS An increase in the Th1 lymphocyte population was associated with more CAD, and an increased Th1/Th2 ratio was found in patients with NSTEMI and STEMI (controls 7.27±2.98; stable CAD 7.58±2.52; NSTEMI 16.62±2.74; and STEMI 22.32±7.35) (P<0.001). The proportion of Th1 cells and the Th1/Th2 ratio increased as the number of affected arteries, the degree of stenosis, and the lesion length increased. At a median follow-up of 18.2 months, patients with CAD and an increased Th1/Th2 ratio had a significant increase in adverse cardiac events compared with patients with a reduced Th1/Th2 ratio (log-rank, P=0.042). CONCLUSIONS An increased ratio of circulating Th1 to Th2 cells in patients with AMI was associated with the severity of CAD determined by angiography.

[Related biomarkers in the diagnosis of prostate cancer].

Prostate cancer is one of the most common malignant tumors in the male urinary system as well as the second leading cause of cancer death in men. Prostate specific antigen (PSA) screening is the main method for the early diagnosis of prostate cancer, but has a low specificity for its detection. In recent years, a variety of tumor markers with high sensitivity and specificity have been found. This review focuses on some of the more promising tumor biomarkers such as prostate cancer antigen 3, early prostate cancer antigen, prostate-specific membrane antigen, alpha-methylacyl-CoA racemase, and vascular endothelial growth factor.

Multimodal ultrasound imaging for diagnostic differentiation of sclerosing adenosis from invasive ductal carcinoma.

Background: Sclerosing adenosis (SA) is a common proliferative benign lesion without atypia in the breast that may mimic invasive ductal carcinoma (IDC) on medical imaging, leading to it often being misdiagnosed and mistreated. Consequently, the purpose of this study was to assess the diagnostic value of multimodal ultrasound imaging in distinguishing SA from IDC. Methods: Multimodal ultrasound imaging, including automated breast volume scan (ABVS), elasticity imaging (EI), and color Doppler flow imaging (CDFI), were performed on 120 consecutive patients comprising 122 breast lesions (54 SA, 68 IDC). All lesions were pathologically confirmed. Multimodal ultrasound imaging features were compared between the two groups. Binary logistic regression analysis based on ABVS, EI, and CDFI was conducted to formulate a logistic regression equation for differentiating SA from IDC. The diagnostic performances of ABVS, EI, CDFI, and their combination were compared by the receiver operating characteristic (ROC) curve analysis. Results: The sensitivity, specificity, and accuracy of ABVS, EI, CDFI, and their combination in differentiating SA from IDC were, respectively, 75.00%, 72.22%, and 73.77%; 86.76%, 72.22%, and 80.33%; 73.53%, 64.81%, and 69.67%; and 88.24%, 74.07%, and 81.97%. Combining multimodal ultrasound imaging yielded an area under the curve (AUC) of 0.895 (95% confidence interval: 0.827-0.943), which was higher than that of ABVS, EI, and CDFI, with AUC values of 0.736, 0.795, and 0.692, respectively, and the difference was statistically significant (ABVS vs. combined model, P<0.001; CDFI vs. combined model, P<0.001; EI vs. combined model, P<0.001). There was no significant difference in the diagnostic efficacy among the three imaging modalities (ABVS vs. EI, P=0.266; ABVS vs. CDFI, P=0.4671; EI vs. CDFI, P=0.051). Compared with those in IDC, the calcification (16.67% vs. 57.35%; P<0.001) and retraction phenomena in the coronal planes (18.52% vs. 57.35%; P<0.001) were less common in patients with SA, while circumscribed margin (38.89% vs. 5.88%; P<0.001), vascularity grade 0-I (64.81% vs. 26.47%; P<0.001), and elasticity scores 1-3 (72.22% vs. 13.24%; P<0.001) were more frequently found in patients with SA. Patients with SA were significantly younger than were patients with IDC (43±11 vs. 54±11 years; P<0.001), and the lesion size was smaller in patients with SA than in those with IDC (median size 1.0 cm; interquartile range (IQR), 0.9 cm vs. median size 1.3 cm; IQR, 1.3 cm; P<0.001). Conclusions: The preliminary results suggested that multimodal ultrasound imaging can improve the diagnostic accuracy of SA and provide additional information for differential diagnosis of SA and IDC.

Polymer Donor with a Simple Skeleton and Minor Siloxane Decoration Enables 19% Efficiency of Organic Solar Cells.

Development of polymer donors with simple chemical structure and low cost is of great importance for commercial application of organic solar cells (OSCs). Here, side-chain random copolymer PMQ-Si605 with a simply 6,7-difluoro-3-methylquinoxaline-thiophene backbone and 5% siloxane decoration of side chain is synthesized in comparison with its alternating copolymer PTQ11. Relative to molecular weight (Mn) of 28.3 kg mol-1 for PTQ11, the random copolymer PMQ-Si605 with minor siloxane decoration is beneficial for achieving higher Mn up to 51.1 kg mol-1. In addition, PMQ-Si605 can show stronger aggregation ability and faster charge mobility as well as more efficient exciton dissociation in active layer as revealed by femtosecond transient absorption spectroscopy. With L8-BO-F as acceptor, its PMQ-Si605 based OSCs display power conversion efficiency (PCE) of 18.08%, much higher than 16.21% for PTQ11 based devices. With another acceptor BTP-H2 to optimize the photovoltaic performance of PMQ-Si605, further elevated PCEs of 18.50% and 19.15% can be achieved with the binary and ternary OSCs, respectively. Furthermore, PMQ-Si605 based active layers are suitable for processing in high humidity air, an important factor for massive production of OSCs. Therefore, the siloxane decoration on polymer donors is promising, affording PMQ-Si605 as a high-performing and low cost candidate.

Excellent Charge Separation of NCQDs/ZnS Nanocomposites for the Promotion of Photocatalytic H2 Evolution.

Carbon Quantum dots (CQDs) are widely studied because of their good optical and electronic characteristics and because they can easily generate photocarriers. Nitrogen-doped CQDs (NCQDs) may exhibit improved hydrophilic, optical, and electron-transfer properties, which are conducive to photocatalytic hydrogen evolution. In this paper, NCQD-modified ZnS catalysts were successfully prepared. Under the irradiation of the full spectrum, the H2 evolution rate of the optimal catalyst 0.25 wt % NCQDs/ZnS achieves 5.70 mmol g-1 h-1, which is 11.88, 43.84, and 5.14 times the values of ZnS (0.48 mmol g-1 h-1), NCQDs (0.13 mmol g-1 h-1), and CQDs/ZnS (1.11 mmol g-1 h-1), respectively. Furthermore, it shows good stability, indicating that the modification of NCQDs prevents the photocorrosion and oxidation of ZnS. The enhanced performance is due to NCQD loading, which promotes the separation of photogenerated carriers, optimizes the structures, and increases the specific surface area. This work highlights the fact that NCQD-modified ZnS may afford a new strategy to synthesize ZnS-based photocatalysts with enhanced H2 production performance.

Study on the correlation between IL-12p70, IL-17A and migraine in children.

Objective: To compare the serum levels of 12 cytokines in migraine group, encephalitis with headache symptoms group, pneumonia without headache symptoms group and migraine subgroups to explore the cytokines associated with migraine in children and their levels. Methods: A total of 44 children with migraine, 27 children in the encephalitis group with headache symptoms and 44 children in the pneumonia group without headache symptoms were selected from January 2022 to August 2023 in Hebei Children's Hospital. They were all tested for serum cytokines by immunofluorescence assay. The migraine group was further divided into subgroups according to different age, gender, course of disease, and presence of coinfection. The differences of serum cytokine levels among the above groups were compared, and the correlation analysis was carried out. Results: Except IL-5, there were no significant differences in the expression levels of other 11 inflammatory cytokines between migraine subgroups. Compared with encephalitis with headache symptoms group and pneumonia without headache symptoms group the serum levels of IL-4, TNF-α, IL-17A, and IL-12p70 were higher in migraine group than in pneumonia group, and the levels of IL-12p70 were higher than those in encephalitis group (p < 0.05). An increase in serum IL-12p70 (OR = 1.267, 95%CI 1.054-1.523, p = 0.012) and IL-17A (OR = 1.066, 95%CI 1.016-1.119, p = 0.010) levels had a significant effect on migraine. Conclusion: Elevated serum levels of IL-12p70 and IL-17A may increase the risk of migraine in children, which has certain diagnostic and predictive value.

A novel conditional active biologic anti-EpCAM x anti-CD3 bispecific antibody with synergistic tumor selectivity for cancer immunotherapy.

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that plays several roles in cancer biology. EpCAM is an attractive therapeutic target because of its expression in most solid tumors. However, targeting EpCAM has been challenging because it is also highly expressed in normal epithelial tissues. Initial attempts to develop EpCAM-specific T-cell engagers were unsuccessful due to severe cytokine release effects, as well as serious on-target, off-tumor drug-related toxicities. We developed novel, conditionally active biological (CAB) bispecific antibodies that bind to both EpCAM and CD3 in an acidic tumor microenvironment. In healthy tissues, binding to EpCAM and CD3 is greatly reduced by a novel, dual CAB selection, where each binding domain is independently blocked by the presence of physiological chemicals known as Protein-associated Chemical Switches (PaCS). The CAB anti-EpCAM T-cell engagers displayed the anticipated bispecific binding properties and mediated the potent lysis of EpCAM-positive cancer cell lines through the recruitment of T cells in the tumor microenvironment. Xenograft studies showed that the efficacy of CAB bispecific antibodies is similar to that of a non-CAB anti-EpCAM bispecific antibody, but they have markedly reduced toxicity in non-human primates, indicating an unprecedentedly widened therapeutic index of over 100-fold. These preclinical results indicate that the dual CAB bispecific antibody is potentially both a powerful and safe therapeutic platform and a promising T cell-engaging treatment for patients with EpCAM-expressing tumors.

Development of a novel conditionally active EpCAM-specific T-cell engager with enhanced safety and tolerability for treatment of solid tumors.

Carbon Quantum Dots-Doped Ni3Se4/Co9Se8/Fe3O4 Multilayer Nanosheets Prepared Using the One-Step Solvothermal Method to Boost Electrocatalytic Oxygen Evolution.

Oxygen evolution reaction is a momentous part of electrochemical energy storage and conversion devices such as rechargeable metal-air batteries. It is particularly urgent to develop low-cost and efficient electrocatalysts for oxygen evolution reactions. As a potential substitute for noble metal electrocatalysts, transition metal selenides still prove challenging in improving the activity of oxygen evolution reaction and research into reaction intermediates. In this study, a simple one-step solvothermal method was used to prepare a polymetallic compound carbon matrix composite (Co9Se8/Ni3Se4/Fe3O4@C) with a multilayered nanosheets structure. It exhibited good OER activity in an alkaline electrolyte solution, with an overpotential of 268 mV at 10 mA/cm2. In addition, this catalyst also showed excellent performance in the 24 h stability test. The composite presents a multi-layer sheet structure, which effectively improves the contact between the active site and the electrolyte. The selenide formed by Ni and Co has a synergistic effect, and Fe3O4 and Co9Se8 form a heterojunction structure which can effectively improve the reaction activity by initiating the electronic coupling effect through the interface modification. In addition, carbon quantum dots have rich heteroatoms and electron transferability, which improves the electrochemical properties of the composites. This work provides a new strategy for the preparation of highly efficient OER electrocatalysts utilizing the multi-metal synergistic effect.

Efficient photocatalytic hydrogen production by space separation of photo-generated charges from S-scheme ZnIn2S4/ZnO heterojunction.

ZnIn2S4/ZnO heterostructures have been achieved by a simple in-situ growth solvothermal method. Under full spectrum irradiation, the optimal photocatalyst 2ZnIn2S4/ZnO exhibits H2 evolution rate of 13,638 (water/ethanol = 1:1) and 3036 (water) µmol·g-1h-1, which is respectively 4 and 5 times higher than that of pure ZnIn2S4. In situ illumination X-ray photoelectron spectroscopy (ISI-XPS) analysis and density functional theory (DFT) calculations show that the electrons of ZnIn2S4 are removed to ZnO through hybridization and form an internal electric field between ZnIn2S4 and ZnO. The optical properties of the catalyst and the effect of internal electric field (IEF) can increase photo-generated electrons (e-)-holes (h+) transport rate and enhance light collection, resulting in profitable photocatalytic properties. The photoelectrochemical and EPR results show that a stepped (S-scheme) heterojunction is formed in the ZnIn2S4/ZnO redox center, which greatly promotes separation of e--h+ pairs and efficient H2 evolution. This research offers an effective method for constructing an efficient S-Scheme photocatalytic system for H2 evolution.

[MicroRNA-499 improved septic myocardial dysfunction by regulating myosin heavy chain gene axis].

OBJECTIVE: To investigate the role and mechanism of microRNA-499 (miR-499) regulating α-myosin heavy chain (α-MHC) and ß-myosin heavy chain (ß-MHC) gene axis in septic myocardial dysfunction (SMD) and its significance. METHODS: Sixty healthy adult male Sprague-Dawley (SD) rats were divided into phosphate buffered saline (PBS) control group (PBS group), lipopolysaccharide (LPS) induced SMD model group (LPS group), miR-499 agonist pretreatment group (agomir+LPS group), and miR-499 inhibitor pretreatment group (antagomir+LPS group) by random number table, with 15 rats in each group. SMD rat model was reproduced by intraperitoneal injection of LPS 10 mg/kg. The PBS group was intraperitoneally injected with the same amount of PBS. The two pretreatment groups were injected with agomir 30 mg/kg or antagomir 80 mg/kg through the caudal vein for 3 days, once a day. PBS group and LPS group were not pretreated. Echocardiography was detected 5 hours after LPS injection, and relevant indexes were recorded. The expression of miR-499 in plasma and myocardial tissue was detected by real-time quantitative polymerase chain reaction (qPCR). Western blotting was used to detect the protein expressions of α-MHC and ß-MHC in myocardial tissue. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of heart failure, was measured by electrochemiluminescence. RESULTS: Compared with the PBS group, the rats in LPS group were depressed. Additionally, LPS down-regulated the level of miR-499 in plasma and myocardial tissue, decreased α-MHC expression in myocardial tissue and up-regulated the expression of ß-MHC. Echocardiography showed that left ventricular ejection fraction (LVEF), left ventricle fractional shortening (LVFS), cardiac output (CO), stroke volume (SV) and heart rate (HR) decreased by 49.1%, 59.2%, 48.8%, 39.4% and 15.9%, respectively, and the level of plasma NT-proBNP increased significantly in LPS group, indicating that LPS could induce cardiac dysfunction in rats. Compared with the LPS group, after pretreatment with agomir to overexpress the miR-499, LVEF and LVFS were significantly increased [LVEF: 0.662±0.020 vs. 0.323±0.024, LVFS: (36.16±1.43)% vs. (20.20±1.32)%, both P < 0.01], which suggested that the cardiac function of rats was improved in agomir+LPS group. At the same time, pretreatment with agomir significantly down-regulated the ß-MHC protein expression (ß-MHC/GAPDH: 0.74±0.04 vs. 2.97±0.34, P < 0.01), significantly up-regulated α-MHC protein expression (α-MHC/GAPDH: 1.59±0.05 vs. 0.74±0.14, P < 0.01), and significantly decreased the plasma NT-proBNP level (ng/L: 114.49±6.85 vs. 334.13±4.36, P < 0.01). After pretreatment with antagomir to inhibit the expression of miR-499, echocardiography showed that LVEF and LVFS were significantly lower than those in the LPS group [LVEF: 0.297±0.021 vs. 0.323±0.024, LVFS: (19.38±1.52)% vs. (21.20±1.32)%, both P < 0.01], which suggested that the cardiac function of rats was significantly inhibited. At the same time, pretreatment with antagomir significantly down-regulated α-MHC protein expression in myocardial tissue (α-MHC/GAPDH: 0.63±0.03 vs. 0.74±0.14, P < 0.01), significantly up-regulated ß-MHC protein expression (ß-MHC/GAPDH: 3.03±0.47 vs. 2.97±0.34, P < 0.01), and significantly increased the level of plasma NT-proBNP (ng/L: 373.91±4.23 vs. 334.13±4.36, P < 0.05). CONCLUSIONS: miR-499 could regulate the expression of α-MHC and ß-MHC which improved cardiac dysfunction caused by sepsis. Targeted regulation of miR-499 expression may be an effective way to treat SMD.

Multi-Role Surface Modification of Single-Crystalline Nickel-Rich Lithium Nickel Cobalt Manganese Oxides Cathodes with WO3 to Improve Performance for Lithium-Ion Batteries.

Compared with the polycrystalline system, the single-crystalline ternary cathode material has better cycle stability because the only primary particles without grain boundaries effectively alleviate the formation of micro/nanocracks and retain better structural integrity. Therefore, it has received extensive research attention. There is no consistent result whether tungsten oxide acts as doping and/or coating from the surface modification of the polycrystalline system. Meanwhile, there is no report on the surface modification of the single-crystalline system by tungsten oxide. In this paper, multirole surface modification of single-crystalline nickel-rich ternary cathode material LiNi0.6Co0.2Mn0.2O2 by WO3 is studied by a simple method of adding WO3 followed by calcination. The results show that with the change in the amount of WO3 added, single-crystalline nickel-rich ternary cathode material can be separately doped, separately coated, and both doped and coated. Either doping or coating effectively enhances the structural stability, reduces the polarization of the material, and improves the lithium-ion diffusion kinetics, thus improving the cycle stability and rate performance of the battery. Interestingly, both doping and coating (for SC-NCM622-0.5%WO3) do not show a more excellent synergistic effect, while the single coating (for SC-NCM622-1.0%WO3) after eliminating the rock-salt phase layer performs the most excellent modification effect.

Directed Stabilization by Air-Milling and Catalyzed Decomposition by Layered Titanium Carbide Toward Low-Temperature and High-Capacity Hydrogen Storage of Aluminum Hydride.

AlH3 is a metastable hydride with a theoretical hydrogen capacity of 10.01 wt % and is very easy to decompose during ball milling especially in the presence of many catalysts, which will lead to the attenuation of the available hydrogen capacity. In this work, AlH3 was ball milled in air (called "air-milling") with layered Ti3C2 to prepare a Ti3C2-catalyzed AlH3 hydrogen storage material. Such air-milled and Ti3C2-catalyzed AlH3 possesses excellent hydrogen storage performances, with a low initial decomposition temperature of just 61 °C and a high hydrogen release capacity of 8.1 wt %. In addition, 6.9 wt % of hydrogen can be released within 20 min at constantly 100 °C, with a low activation energy as low as 40 kJ mol-1. Air-milling will lead to the formation of an Al2O3 oxide layer on the AlH3 particles, which will prevent continuous decomposition of AlH3 when milling with active layered Ti3C2. The layered Ti3C2 will grip on and intrude into the AlH3 particle oxide layers and then catalyze the decomposition of AlH3 during heating. The strategy employing air-milling as a synthesis method and utilizing layered Ti3C2 as a catalyst in this work can solve the key issue of severe decomposition during ball milling with catalysts economically and conveniently and thus achieve both high-capacity and low-temperature hydrogen storage of AlH3. This air-milling method is also effective for other active catalysts toward both reducing the decomposition temperature and increasing the available hydrogen capacity of AlH3.

Co-Addition of Mg2Si and Graphene for Synergistically Improving the Hydrogen Storage Properties of Mg-Li Alloy.

Mg-Li alloy possesses a high hydrogen capacity. However, the hydrogenation and dehydrogenation performances are still far from practical application. In this work, Mg2Si (MS) and graphene (G) were employed together to synergistically improve the hydrogen storage properties of Mg-Li alloy. The structures of the samples were studied by XRD and SEM methods. The hydrogen storage performances of the samples were studied by nonisothermal and isothermal hydrogenation and dehydrogenation, thermal analysis, respectively. It is shown that the onset dehydrogenation temperature of Mg-Li alloy was synergistically reduced from 360°C to 310°C after co-addition of Mg2Si and graphene. At a constant temperature of 325°C, the Mg-Li-MS-G composite can release 2.7 wt.% of hydrogen within 2 h, while only 0.2 wt.% of hydrogen is released for the undoped Mg-Li alloy. The hydrogenation activation energy of the Mg-Li-MS-G composite was calculated to be 86.5 kJ mol-1. Microstructure and hydrogen storage properties studies show that graphene can act as a grinding aid during the ball milling process, which leads to a smaller particle size for the composites. This work demonstrates that coaddition of Mg2Si and graphene can synergistically improve the hydrogen storage properties of Mg-Si alloy and offers an insight into the role of graphene in the Mg-Li-MS-G composite.

Effect of high pressure homogenization on aggregation, conformation, and interfacial properties of bighead carp myofibrillar protein.

Fish myofibrillar protein is underutilized due to the formation of insoluble aggregates in low salt media. High pressure homogenization (HPH) at 20, 40, and 60 MPa for four passes was applied on bighead carp myofibrillar protein in order to modify its structure and interfacial properties. Changes in aggregation, conformation, solubility, emulsifying and foaming properties of myofibrillar protein were investigated. The aggregates of myofibrillar protein were obviously disrupted by HPH treatment. The size of myofibrillar protein aggregates became smaller and more uniform as the treating pressure increased, accompanied by notable decreases of cross-sectional height and Rq value in AFM image. Furthermore, the conformation of HPH-treated myofibrillar protein was unfolded into a flexible and open structure. α-helix and ß-sheet were converted into ß-turn and random coil. Surface hydrophobicity and zeta potential were strengthened, along with the exposure of sulfhydryl groups onto molecule surface. On the other hand, solubility, emulsifying activity index (EAI) and foaming capacity (FC) of HPH-treated myofibrillar protein were markedly enhanced with the increasing pressure. Especially after HPH treatment at 60 MPa, myofibrillar protein was almost dissolved in low salt media (solubility 91.86%) with 4.92 fold for EAI and 3.52 fold for FC. But there was little variation in emulsifying and foaming stabilities. These results suggested that HPH treatment has interesting potential to induce the dissociation and unfolding of myofibrillar protein in low salt media, therefore improving its interfacial properties. PRACTICAL APPLICATION: Carp myofibrillar protein was treated by high pressure homogenization (HPH). Aggregates of myofibrillar protein were disrupted into smaller size form. Conformation of myofibrillar protein was unfolded into open and loose structure. Emulsifying and foaming capacities of myofibrillar protein were improved. HPH treatment modified the structure and interfacial properties of myofibrillar protein.