As the internet has become popularized in recent years, cognitive behavioral therapy for insomnia (CBT-i) has shifted from a face-to-face approach to delivery via the internet (internet-based CBT-i, ...ICBT-i). Several studies have investigated the effects of ICBT-i on comorbid anxiety and depression; however, the results remain inconclusive. Thus, a meta-analysis was conducted to determine the effects of ICBT-i on anxiety and depression. Electronic databases, including PubMed, EMBASE, PsycINFO and the Cochrane Library (throughout May 28, 2015), were systematically searched for randomized controlled trials (RCTs) of ICBT-i. Data were extracted from the qualified studies and pooled together. The standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to assess the effects of ICBT-i on comorbid anxiety and depression. Nine records that included ten studies were ultimately qualified. The effect sizes (ESs) were -0.35 -0.46, -0.25 for anxiety and -0.36 -0.47, -0.26 for depression, which were stable using a between-group or within-group comparison and suggest positive effects of ICBT-i on both comorbid disorders. Although positive results were identified in this meta-analysis, additional high-quality studies with larger sample sizes are needed in the future.
Cancer metastasis leading to the dysfunction of invaded organs is the main cause of the reduced survival rates in lung cancer patients. However, the molecular mechanism for lung cancer metastasis ...remains unclear. Recently, the increased activity of inflammasome appeared to correlate with the metastatic progression and immunosuppressive ability of various cancer types. Our results showed that the mRNA levels of absence in melanoma 2 (AIM2), one of the inflammasome members, are extensively upregulated in primary tumors compared with normal tissues derived from the TCGA lung adenocarcinoma (LUAD) database. Moreover, Kaplan‐Meier analysis demonstrated that a higher mRNA level of AIM2 refers to a poor prognosis in LUAD patients. Particularly, AIM2 upregulation is closely correlated with smoking history and the absence of EGFR/KRAS/ALK mutations in LUAD. We further showed that the endogenous mRNA levels of AIM2 are causally associated with the metastatic potentials of the tested LUAD cell lines. AIM2 knockdown suppressed but overexpression promoted the migration ability and lung colony–forming ability of tested LUAD cells. In addition, we found that AIM2 upregulation is closely associated with an increased level of immune checkpoint gene set, as well as programmed cell death‐ligand 1 (PD‐L1) transcript, in TCGA LUAD samples. AIM2 knockdown predominantly repressed but overexpression enhanced PD‐L1 expression via altering the activity of PD‐L1 transcriptional regulators NF‐κB/STAT1 in LUAD cells. Our results not only provide a possible mechanism underlying the AIM2‐promoted metastatic progression and immune evasion of LUAD but also offer a new strategy for combating metastatic/immunosuppressive LUAD via targeting AIM2 activity.
The illustration of a possible mechanism for the AIM2‐fostered EMT progression and PD‐L1 expression in the metastatic/immunosuppressive lung adenocarcinoma. AIM2 increases PD‐L1 expression via activating its transcriptional regulators NF‐kB/STAT1.
Hepatocellular carcinoma (HCC) is a heterogeneous cancer required combination therapy, such as photothermal therapy and chemotherapy. In recent years, cancer immunotherapies are rapidly evolving and ...are some of the most promising avenues to approach malignancies. Thus, the combination of the traditional therapies and immunotherapy in one platform may improve the efficacy for HCC treatment.
In this work, we have prepared a black phosphorus (BP)-Au-thiosugar nanosheets (BATNS), in which Au-thiosugar coating and functionalization improved the stability of both black phosphorus nanosheets (BPNS) and gold ions in different simulated physiological environments. The compression of the BATNS band gap can convert more photon energy to heat generation compared with BPNS, resulting in higher photothermal conversion efficiency. The in vitro and in vivo results also revealed a stronger reduction on the hepatocellular carcinoma of mice and prolonged survival of disease models compared with BPNS. More importantly, BATNS showed an additional immune effect by increasing local NK cell infiltration but not T cell on the liver cancer treatment, and this immune effect was caused by the thermal effect of BATNS photothermal treatment.
The novel BATNS could improve the stability of BPNS and simultaneously combine the cancer thermotherapy and immunotherapy leaded by local NK cell infiltration, resulting in a better therapeutic efficacy on hepatocellular carcinoma. This work also provided a new path to design BP-based materials for biomedical applications.
The semiconductor direct‐current triboelectric nanogenerator (SDC‐TENG) based on the tribovoltaic effect is promising for developing a new semiconductor energy technology with high power density. ...Here, the first SDC‐TENG built using gallium nitride (GaN) and bismuth telluride (Bi2Te3) for ultrahigh‐power generation is reported. During the friction process, an additional interfacial electric field is formed by continuous contact electrification (CE), and abundant electron–hole pairs are excited and move directionally to form a junction current that is always internally from Bi2Te3 to GaN, regardless of the semiconductor type. The peak open‐circuit voltage can reach up to 40 V and the power density is 11.85 W m−2 (average value is 9.23 W m−2), which is approximately 200 times higher than that of previous centimeter‐level SDC‐TENGs. Moreover, compared to traditional polymer TENGs under the same conditions, the average power density is remarkably improved by over 40 times. This study provides the first evidence of CE on the tribovoltaic effect and sets the normalized power density record for TENGs, which demonstrates a great potential of the tribovoltaic effect for energy harvesting and sensing.
The first semiconductor direct‐current triboelectric nanogenerator (SDC‐TENG) using gallium nitride and bismuth telluride is designed for ultrahigh power generation (40 V, 2.56 A m−2, 11.85 W m−2). Compared to traditional polymer TENGs and previous centimeter‐level SDC‐TENGs, this work sets the normalized power density record for TENGs, which demonstrates the great potential of the tribovoltaic effect for energy harvesting and sensing.
Radioresistance and lymph node metastasis are common phenotypes of refractory oral squamous cell carcinoma (OSCC). As a result, understanding the mechanism for radioresistance and metastatic ...progression is urgently needed for the precise management of refractory OSCC. Recently, immunotherapies, e.g. immune checkpoint inhibitors (ICIs), were employed to treat refractory OSCC; however, the lack of predictive biomarkers still limited their therapeutic effectiveness.
The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) databases and RT-PCR analysis were used to determine absent in melanoma 2 (AIM2) expression in OSCC samples. Colony-forming assay and trans-well cultivation was established for estimating AIM2 function in modulating the irradiation resistance and migration ability of OSCC cells, respectively. RT-PCR, Western blot and flow-cytometric analyses were performed to examine AIM2 effects on the expression of programmed death-ligand 1 (PD-L1) expression. Luciferase-based reporter assay and site-directed mutagenesis were employed to determine the transcriptional regulatory activity of Signal Transducer and Activator of Transcription 1 (STAT1) and NF-κB towards the AIM2-triggered PD-L1 expression.
Here, we found that AIM2 is extensively upregulated in primary tumors compared to the normal adjacent tissues and acts as a poor prognostic marker in OSCC. AIM2 knockdown mitigated, but overexpression promoted, radioresistance, migration and PD-L1 expression via modulating the activity of STAT1/NF-κB in OSCC cell variants. AIM2 upregulation significantly predicted a favorable response in patients receiving ICI treatments.
Our data unveil AIM2 as a critical factor for promoting radioresistance, metastasis and PD-L1 expression and as a potential biomarker for predicting ICI effectiveness on the refractory OSCC.
Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor ...(GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and
H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.
Conotoxins are small disulfide-rich neurotoxic peptides, which can bind to ion channels with very high specificity and modulate their activities. Over the last few decades, conotoxins have been the ...drug candidates for treating chronic pain, epilepsy, spasticity, and cardiovascular diseases. According to their functions and targets, conotoxins are generally categorized into three types: potassium-channel type, sodium-channel type, and calcium-channel types. With the avalanche of peptide sequences generated in the postgenomic age, it is urgent and challenging to develop an automated method for rapidly and accurately identifying the types of conotoxins based on their sequence information alone. To address this challenge, a new predictor, called iCTX-Type, was developed by incorporating the dipeptide occurrence frequencies of a conotoxin sequence into a 400-D (dimensional) general pseudoamino acid composition, followed by the feature optimization procedure to reduce the sample representation from 400-D to 50-D vector. The overall success rate achieved by iCTX-Type via a rigorous cross-validation was over 91%, outperforming its counterpart (RBF network). Besides, iCTX-Type is so far the only predictor in this area with its web-server available, and hence is particularly useful for most experimental scientists to get their desired results without the need to follow the complicated mathematics involved.
Accumulating lines of evidence indicate that reactive oxygen species (ROS) are important signalling molecules for various cellular processes. 8-Oxo-7,8-dihydroguanine (OG) is a prominent oxidative ...modification formed in DNA by ROS. Recently, it has been proposed that OG may have regulatory and possibly epigenetic-like properties in modulating gene expression by interfering with transcription components or affecting the formation of G-quadruplex structures. Deciphering the molecular mechanisms of OG on regulation of gene expression requires uncovering the location of OG on genome. In the current study, we characterized two commercially available DNA polymerases,
DNA polymerase (
Pol) and
DNA polymerase (
Pol), which can selectively incorporate adenine (A) and cytosine (C) opposite OG, respectively. By virtue of the differential coding properties of
Pol and
Pol that can faithfully or error-prone copy a DNA strand carrying OG, we achieved quantitative and single-base resolution analysis of OG in synthesized DNA that carries OG as well as in the G-rich telomeric DNA from HeLa cells. In addition, the parallel analysis of the primer extension products with
Pol and
Pol followed by sequencing provided distinct detection of OG in synthesized DNA. Future application of this approach will greatly increase our knowledge of the chemical biology of OG with respect to its epigenetic-like regulatory roles.
Dearomative spirocyclization reactions represent a promising means to convert arenes into three‐dimensional architectures; however, controlling the regioselectivity of radical dearomatization with ...nonactivated arenes to afford the spirocyclizative 1,2‐difunctionalization other than its kinetically preferred 1,4‐difunctionalization is exceptionally challenging. Here we disclose a novel strategy for dearomative 1,2‐ or 1,4‐amidoximation of (hetero)arenes enabled by direct visible‐light‐induced homolysis of N−NO bonds of nitrosamides, giving rise to various highly regioselective amidoximated spirocycles that previously have been inaccessible or required elaborate synthetic efforts. The mechanism and origins of the observed regioselectivities were investigated by control experiments and density functional theory calculations.
Reported is a novel method to realize a highly regioselective dearomative difunctionalization for the synthesis of various spirocycles. The nonredox homolysis, the reversible radical coupling, and the nitroso‐oxime tautomerism promote the chemoselectivity of dearomative 1,2‐ or 1,4‐amidoximation.
Diabetes mellitus has become a serious and growing public health concern. It has high morbidity and mortality because of its complications, such as diabetic nephropathy, diabetic cardiovascular ...complication, diabetic neuropathy, diabetic retinopathy, and diabetic hepatopathy. Epidemiological studies revealed that the consumption of tea was inversely associated with the risk of diabetes mellitus and its complications. Experimental studies demonstrated that tea had protective effects against diabetes mellitus and its complications via several possible mechanisms, including enhancing insulin action, ameliorating insulin resistance, activating insulin signaling pathway, protecting islet β-cells, scavenging free radicals, and decreasing inflammation. Moreover, clinical trials also confirmed that tea intervention is effective in patients with diabetes mellitus and its complications. Therefore, in order to highlight the importance of tea in the prevention and management of diabetes mellitus and its complications, this article summarizes and discusses the effects of tea against diabetes mellitus and its complications based on the findings from epidemiological, experimental, and clinical studies, with the special attention paid to the mechanisms of action.
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