Disorder-tuned conductivity in amorphous monolayer carbon.

Correlating atomic configurations-specifically, degree of disorder (DOD)-of an amorphous solid with properties is a long-standing riddle in materials science and condensed matter physics, owing to difficulties in determining precise atomic positions in 3D structures1-5. To this end, 2D systems provide insight to the puzzle by allowing straightforward imaging of all atoms6,7. Direct imaging of amorphous monolayer carbon (AMC) grown by laser-assisted depositions has resolved atomic configurations, supporting the modern crystallite view of vitreous solids over random network theory8. Nevertheless, a causal link between atomic-scale structures and macroscopic properties remains elusive. Here we report facile tuning of DOD and electrical conductivity in AMC films by varying growth temperatures. Specifically, the pyrolysis threshold temperature is the key to growing variable-range-hopping conductive AMC with medium-range order (MRO), whereas increasing the temperature by 25 °C results in AMC losing MRO and becoming electrically insulating, with an increase in sheet resistance of 109 times. Beyond visualizing highly distorted nanocrystallites embedded in a continuous random network, atomic-resolution electron microscopy shows the absence/presence of MRO and temperature-dependent densities of nanocrystallites, two order parameters proposed to fully describe DOD. Numerical calculations establish the conductivity diagram as a function of these two parameters, directly linking microstructures to electrical properties. Our work represents an important step towards understanding the structure-property relationship of amorphous materials at the fundamental level and paves the way to electronic devices using 2D amorphous materials.

Assessing the Role of BN-Embedding Position in B2N2-Perylenes.

Incorporating heteroatoms can effectively modulate the molecular optoelectronic properties. However, the fundamental understanding of BN doping effects in BN-embedded polycyclic aromatic hydrocarbons (PAHs) is underexplored, lacking rational guidelines to modulate the electronic structures through BN units for advanced materials. Herein, a concise synthesis of novel B2N2-perylenes with BN doped at the bay area is achieved to systematically explore the doping effect of BN position on the photophysical properties of PAHs. The shift of BN position in B2N2-perylenes alters the π electron conjugation, aromaticity and molecular rigidness significantly, achieving substantially higher electron transition abilities than those with BN doped in the nodal plane. It is further clarified that BN position dominates the photophysical properties over BN orientation. The revealed guideline here may apply generally to novel BN-PAHs, and aid the advancement of BN-PAHs with highly-emissive performance.

Irisin alters D-galactose-induced apoptosis by increasing caveolin-1 expression in C2C12 myoblasts and skeletal muscle fibroblasts.

Muscle atrophy and skeletal muscle fibrosis are significant pathological manifestations of primary sarcopenia. The regulation of C2C12 myoblast and skeletal muscle fibroblast apoptosis is associated with these pathological changes. Previous studies have indicated that irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), can alleviate primary sarcopenia. However, the mechanisms of the effect of irisin in age-related apoptosis remain unknown. Our present research aimed to explore the effect of irisin and the underlying mechanism of D-galactose (D-gal)-induced apoptosis in skeletal muscle fibroblasts and C2C12 myoblasts. We found the opposite effects of D-gal on C2C12 myoblasts and fibroblasts. We also found that irisin suppressed C2C12 cell apoptosis and promoted fibroblast apoptosis. Mechanistically, irisin altered D-gal-induced apoptosis by increasing caveolin-1 expression. Taken together, these findings further demonstrated that irisin is a potential agent that can treat aged-relative muscle atrophy and fibrosis.

"Spine Surgery" of Perylene Diimides with Covalent B-N Bonds toward Electron-Deficient BN-Embedded Polycyclic Aromatic Hydrocarbons.

BN-embedded polycyclic aromatic hydrocarbons (PAHs) with unique optoelectronic properties are underdeveloped relative to their carbonaceous counterparts due to the lack of suitable and facile synthetic methods. Moreover, the dearth of electron-deficient BN-embedded PAHs further hinders their application in organic electronics. Here we present the first facile synthesis of novel perylene diimide derivatives (B2N2-PDIs) featuring n-type B-N covalent bonds. The structures of these compounds are fully confirmed through the detailed characterizations with NMR, MS, and X-ray crystallography. Further investigation shows that the introduction of BN units significantly modifies the photophysical and electronic properties of these B2N2-PDIs and is further understood with the aid of theoretical calculations. Compared with the parent perylene diimides (PDIs), B2N2-PDIs exhibit deeper highest occupied molecular orbital energy levels, new absorption peaks in the high-energy region, hypsochromic shift of absorption and emission maxima, and decrement of photoluminescent quantum yields. Single-crystal field-effect transistors based on B2N2-PDIs showcase an electron mobility up to 0.35 cm2 V-1 s-1, demonstrating their potential application in optoelectronic materials.

Parent B2 N2 -Perylenes with Different BN Orientations.

Introducing BN units into polycyclic aromatic hydrocarbons expands the chemical space of conjugated materials with novel properties. However, it is challenging to achieve accurate synthesis of BN-PAHs with specific BN positions and orientations. Here, three new parent B2 N2 -perylenes with different BN orientations are synthesized with BN-naphthalene as the building block, providing systematic insight into the effects of BN incorporation with different orientations on the structure, (anti)aromaticity, crystal packing and photophysical properties. The intermolecular dipole-dipole interaction shortens the π-π stacking distance. The crystal structure, (anti)aromaticity, and photophysical properties vary with the change of BN orientation. The revealed BN doping effects may provide a guideline for the synthesis of BN-PAHs with specific stacking structures, and the synthetic strategy employed here can be extended toward the synthesis of larger BN-embedded PAHs with adjustable BN patterns.

Imide-Fused Diazatetracenes: Synthesis, Characterization, and Application in Perovskite Solar Cells.

A series of imide-fused diazatetracenes were synthesized via Buchwald-Hartwig C-N coupling with a highly active palladium source. The introduction of an imide segment effectively lowers the LUMO levels compared with that of unsubstituted diazatetracene. By adjusting the alkyl chains of the diazatetracenes, different solid-state packings were achieved, resulting in distinct photoluminescent behaviors. Their electron-transporting properties were demonstrated in the proof-of-concept Perovskite solar cells as electron transporting layers.

U-Shaped Helical Azaarenes: Synthesis, Structures, and Properties.

The synthesis and properties of a series of U-shaped helical azaarenes are reported. Crystal structures of these helical azaarenes were obtained, and the solid-state structures unequivocally exhibited their helicity.

Unexpected Synthesis, Properties, and Nonvolatile Memory Device Application of Imidazole-Fused Azaacenes.

The unexpected synthesis and characterization of imidazole-fused azaacenes are presented. Their optical and electrochemical properties have been investigated and compared with these of previously reported imidazole-fused azaacenes. Application of these two imidazole-fused azaacenes in memory devices showed distinctly different resistive behaviors.

Efficient Inverted Perovskite Solar Cells by Employing N-Type (D-A1 -D-A2 ) Polymers as Electron Transporting Layer.

It is highly desirable to employ n-type polymers as electron transporting layers (ETLs) in inverted perovskite solar cells (PSCs) due to their good electron mobility, high hydrophobicity, and simplicity of film forming. In this research, the capability of three n-type donor-acceptor1 -donor-acceptor2 (D-A1 -D-A2 ) conjugated polymers (pBTT, pBTTz, and pSNT) is first explored as ETLs because these polymers possess electron mobilities as high as 0.92, 0.46, and 4.87 cm2 (Vs)-1 in n-channel organic transistors, respectively. The main structural difference among pBTT, pBTTz, and pSNT is the position of sp2 -nitrogen atoms (sp2 -N) in the polymer main chains. Therefore, the effect of different substitution positions on the PSC performances is comprehensively studied. The as-fabricated p-i-n PSCs with pBTT, pBTTz, and pSNT as ETLs show the maximum photoconversion efficiencies of 12.8%, 14.4%, and 12.0%, respectively. To be highlighted, pBTTz-based device can maintain 80% of its stability after ten days due to its good hydrophobicity, which is further confirmed by a contact angle technique. More importantly, the pBTTz-based device shows a neglected hysteresis. This study reveals that the n-type polymers can be promising candidates as ETLs to approach solution-processed highly-efficient inverted PSCs.

High glucose-induced defective thrombospondin-1 release from astrocytes via TLR9 activation contributes to the synaptic protein loss.

Diabetes, characterized by chronic hyperglycemia, is known to induce synaptic degeneration in the brain, thereby resulting in cognitive dysfunction. Thrombospondin-1(TSP-1), the secreted protein produced by astrocytes, plays a crucial role in promoting synapse formation. Toll-like receptor 9 (TLR9) has been widely known to initiate the innate immune response. We recently reported TLR9 activation in neurons results in tau hyperphosphorylation induced by HG in vitro. Its activation has been also considered to mediate oxidative stress and astrocytic dysfunction under pathological circumstance. However, whether astrocytic TSP-1 alteration plays a role in synaptic protein loss under high glucose condition and whether TLR9 activation is involved in this process have not been reported. In this study, we found that primary mouse astrocytes incubated in high glucose (30mM) induced a significant decreased TSP-1 secretion and increased intracellular contents of TSP-1 without affecting transcription level. Addition of conditioned medium from high glucose (30mM) treated astrocytes to the primary neurons exhibited reduced synaptic proteins expression, which was attenuated by treatment with exogenous rTSP-1. In addition, we demonstrated that TLR9 activation along with reactive oxygen species (ROS) generation in astrocytes was induced by high glucose (30mM). Furthermore, we explored the relationship between TLR9 activation and TSP-1 production. Both TLR9 deficiency and the antioxidant N-acetyl-L-cysteine treatment improved altered intra- and extracellular TSP-1 levels under high glucose condition. Together, our findings suggest that high glucose (30mM) impairs TSP-1 secretion from astrocytes, which depends on astrocytic dysfunction associated with TLR9 activation mediated ROS signaling, ultimately contributing to the synaptic proteins loss.

High glucose-induced complement component 3 up-regulation via RAGE-p38MAPK-NF-κB signalling in astrocytes: In vivo and in vitro studies.

Diabetes is considered as a risk for cognitive decline, which is characterized by neurodegenerative alteration and innate immunity activation. Recently, complement 3 (C3), the critical central component of complement system, has been reported to play a key role in neurodegenerative alterations under pathological condition. Receptor for advanced glycation end products (RAGE) activation is confirmed to mediate several inflammatory cytokines production. However, whether C3 activation participates in the diabetic neuropathology and whether this process is regulated by RAGE activation remains unknown. The present study aimed to investigate the role of C3 in streptozotocin-induced diabetic mice and high glucose-induced primary astrocytes and the underlying modulatory mechanisms. The decreased synaptophysin density and increased C3 deposition at synapses were observed in the diabetic brain compared to the control brain. Furthermore, the elevated C3 was co-localized with GFAP-positive astrocytes in the diabetic brain slice in vivo and high glucose-induced astrocytes culture in vitro. Diabetes/high glucose-induced up-regulation of C3 expression at gene, protein and secretion levels, which were attenuated by pre-treatment with RAGE, p38MAPK and NF-κB inhibitors separately. These results demonstrate that high glucose induces C3 up-regulation via RAGE- p38MAPK-NF-κB signalling in vivo and in vitro, which might be associated with synaptic protein loss.

High-glucose induces tau hyperphosphorylation through activation of TLR9-P38MAPK pathway.

Diabetic encephalopathy (DE) is one of the most common complications of diabetes. The major pathological variations include neurofibrillary tangles (NFTs), which are caused by tau hyperphosphorylation, and senile plaques (SPs) consisting of amyloid ß- protein(Aß) deposits. In recent years, DE research studies have focused on exploring the activation of the inflammatory signaling pathway in immune cells. Toll-like receptor 9 (TLR9) is well known to regulate the inflammatory reactions in immune processes. During the tau hyperphosphorylation process, TLR9 in microglia plays bidirectional roles. However, no studies have clearly demonstrated the relationship between TLR9 and tau hyperphosphorylation in neurons. Based on our experiments, we found significant increase in TLR9 expression in neurons and an increase in tau hyperphosphorylation in high-glucose media. However, these alterations can be reversed by TLR9 inhibitor. Furthermore, we specifically inhibited the activation of P38mitogenactivated protein kinase(P38MAPK) and found an effective decrease in tau hyperphosphorylation. This effect is likely related to Unc93b1. Meanwhile, High glucose levels can induce neuronal apoptosis via the TLR9 signaling pathway. Our studies are the first to reveal that high glucose can regulate tau hyperphosphorylation and neuronal apoptosis via TLR9-P38MAPK signaling pathway. These findings provide a new method for studying the mechanism underlying DE.

Depression as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies.

BACKGROUND: This study examined whether depression was a risk factor for onset of dementia including Alzheimer's disease (AD), vascular dementia (VD) and any dementia, and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. METHODS: EMBASE and MEDLINE were searched for articles published up to February 2011. All studies that examined the relationship between depression and the onset of dementia or MCI were included. Pooled relative risk was calculated using fixed-effects models. RESULTS: Twelve studies met our inclusion criteria for this meta-analysis. All subjects were without dementia or MCI at baseline. Four, two, five, and four studies compared the incidence of AD, VD, any dementia, and MCI between subjects with or without depression, respectively. After pooling all the studies, subjects with depression had higher incidence of AD (relative risk (RR):1.66, 95% confidence interval (CI): 1.29-2.14), VD (RR: 1.89, 95% CI: 1.19-3.01), any dementia (RR: 1.55, 95% CI: 1.31-2.83), and MCI (RR: 1.97, 95% CI: 1.53-2.54) than those without depression. CONCLUSIONS: The quantitative meta-analysis showed that depression was a major risk factor for incidence of dementia (including AD, VD, and any dementia) and MCI.

Irisin ameliorates D-galactose-induced skeletal muscle fibrosis via the PI3K/Akt pathway.

Primary sarcopenia is a multicausal skeletal muscle disease associated with muscle strength and mass loss. Skeletal muscle fibrosis is one of the significant pathological manifestations associated with the development of age-related sarcopenia. Irisin, which is cleaved by the extracellular domain of fibronectin type Ⅲ domain-containing protein 5 (FNDC5), has previously been reported to exert antifibrotic effects on the heart, liver, and pancreas, but whether it can rescue skeletal muscle fibrosis remains unknown. In this study, we examined the effects of irisin on D-galactose (D-gal)-induced skeletal muscle fibroblasts. We found that D-gal-induced senescence, fibrosis, and redox imbalance were inhibited by irisin treatment. Mechanistically, irisin or FNDC5 overexpression attenuated D-gal-induced senescence, redox imbalance, and fibrosis by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Overall, irisin might be a promising therapeutic candidate for age-related skeletal muscle fibrosis.

Age and risk for depression among the elderly: a meta-analysis of the published literature.

OBJECTIVE: The goal of this study was to determine the relationship between age and risk for depression among the old and the oldest old. Method MEDLINE, EMBASE, and the Cochrane Library database were used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study), or incident cases (for longitudinal study) of depression in each age group were extracted and entered into Review Manager 4.2 software. Qualitative meta-analyses of cross-sectional studies and of longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: The qualitative meta-analyses showed that, compared with younger participants (above vs. below 65 years, above vs. below 70 years, above vs. below 75 years, and above vs. below 80 years), older age groups had a significantly higher risk for depression. (All of the ORs and RRs were significant.) Compared with participants aged 55-89, those aged above 90 years had no higher risk for depression. (Neither the OR nor the RR was significant.) CONCLUSIONS: Despite the methodological limitations of this meta-analysis, older age appears to be an important risk factor for depression in the general elderly population (aged below 80 years), but not in the oldest population (aged above 85 years).

Ghrelin-attenuated cognitive dysfunction in streptozotocin-induced diabetic rats.

Diabetic encephalopathy is clinically characterized by acquired behavior and cognitive dysfunction but its pathogenesis is not clear. This study aimed to explore the pathogenesis of diabetic encephalopathy and the mechanisms of ghrelin to ameliorate cognitive dysfunction in diabetic rats. Thirty-six streptozotocin diabetic rat models were established; 12 weeks later, all the rats were randomly divided into 3 groups [diabetic model group (D), ghrelin treatment group (T1), and ghrelin and D-lys-3-GHRP-6 treatment group (T2)] of 12 each. Twelve normoglycemic rats were classified in the normal group (N). Learning and memory behaviors were measured using a spatial version of the Morris water maze test. The brain-derived neurotrophic factor (BDNF), cAMP responsive element binding protein (CREB), phosphorylated CREB (p-CREB), phosphorylated ERK1/2 (p-ERK1/2), caspase-3, and Bcl-xl protein expressions in the hippocampi of all the rats were detected using immunohistochemistry. The mRNA expressions of BDNF, CREB, and caspase-3 were examined using reverse transcription-polymerase chain reaction. The hippocampus neuronal apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling method. We found that learning and memory level in the ghrelin treatment group improved significantly, expression of Bcl-xl, BDNF, CREB, p-CREB, and p-ERK1/2 in the hippocampus was increased in the ghrelin treatment group, and the number of apoptotic neurons in the hippocampus decreased remarkably. Our results showed that the changes of BDNF, CREB, and hippocampus neuronal apoptosis might be involved in the pathogenesis of diabetic encephalopathy. We suggested that ghrelin improved cognitive ability in streptozotocin-induced diabetic rats by improving the expressions of BDNF and CREB and by attenuating hippocampus neuronal apoptosis. The effects of ghrelin depend on the receptor of ghrelin, GHSR-1a, and ERK1/2 pathway.

Fibrinogen, fibrin degradation products and risk of sarcopenia.

BACKGROUND & AIMS: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. METHODS: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. RESULTS: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 µg/mL vs 1.00 µg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (ß: -0.164, p = 0.008), and muscle strength (ß: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 µg/mL, respectively. CONCLUSIONS: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

Beyond Perovskite Solar Cells: Tellurium Iodide as a Promising Light-Absorbing Material for Solution-Processed Photovoltaic Application.

Searching new light-absorbing materials to replace toxic lead halide in solar cells is very important and highly desirable. In this research, we firstly demonstrated that tellurium iodide (TeI4 ) could be used as a light-absorbing material in solar cells due to its suitable optical band gap and the active lone-pair electron orbital in Te4+ . The best power conversion efficiency (PCE=3.56%) was achieved with a concentration of 0.9 M TeI4 in DMF:DMSO (4 : 1, v,v) without any heat treatment or antisolvent dripping. Our study indicates the promising potential of TeI4 for photovoltaic and optoelectronic applications.

Tunable low-dimensional self-assembly of H-shaped bichromophoric perylenediimide Gemini in solution.

A material with diverse self-assembled morphologies is extremely important and highly desirable because such samples can provide tunable optical and electronic properties, which are critical in applications such as organic photovoltaics, microelectronics and bio-imaging. Moreover, the synthesis and controllable self-assembly of H-shaped bichromophoric perylenediimides (PDIs) are needed to advance these materials in organic photovoltaics, microelectronics and bio-imaging; however, this has remained a great challenge thus far. Here, we successfully synthesize a novel H-shaped bichromophoric PDI Gemini through the palladium-catalyzed coupling reaction. The as-prepared PDI Gemini exhibited unprecedented tunable self-assembly behavior in solution, yielding diverse low-dimensional superstructures, such as one-dimensional (1D) helices, two-dimensional (2D) rectangular nanocrystals, pyramid-shaped parallelograms, ultralarge micro-sheets, and uniform nanospheres, under different self-assembly conditions. Of particular interest, the 2D hierarchical superstructures along with their formation mechanisms represent the first finding in the self-assembly of PDI-based molecules. This study opens a new avenue for tunable self-assembly of conjugated molecules and affords opportunities for the fabrication of novel self-assembled optical and electronic materials based on PDI molecules.

Inhibition of TLR9 attenuates skeletal muscle fibrosis in aged sarcopenic mice via the p53/SIRT1 pathway.

Sarcopenia is an age-related syndrome characterized by a gradual loss of muscle mass and function, but its pathophysiological mechanism remains unclear. Skeletal muscle extracellular matrix (ECM) remodeling is an important pathological change in sarcopenia, and fibrosis is the most obvious manifestation of this change. We found that the expression of the immunoreceptor Toll-like receptor 9 (TLR9) is significantly increased in skeletal muscle in aged mice and is positively related to muscle fibrosis. Moreover, in previous reports, the longevity gene Sirt1 was reported to attenuate ECM deposition and improve muscle function. In this study, we hypothesized that TLR9 modulated skeletal muscle fibrosis via Sirt1. We used TLR9 knockout (TLR9 KO) mice and C57 mice, and grip strength and body composition were compared at different ages. We found that TLR9 knockout significantly attenuated skeletal muscle fibrosis and improved muscle function in aged mice. Furthermore, silent information regulator 1 (Sirt1) activity in mice was inhibited by Ex527, which is a specific inhibitor of Sirt1. Negative Sirt1 regulation via the activation of TLR9-related signaling pathways participated in skeletal muscle fibrosis in the sarcopenic mice, and this process might mediated by the Sirt1/Smad signaling pathway. Our findings revealed that fibrosis changes in the gastrocnemius muscle in sarcopenic mice are closely related to TLR9 activation, and TLR9 modulation could be a therapeutic strategy for combating sarcopenia during aging.