Restricted by the poor ability of polymers to dissociate lithium salts and transport ions, solid‐state polymer electrolytes (SPEs) show extremely low ionic conductivities (≈10−7–10−5 S cm−1) and ...transference number of lithium ions (tLi+ ≈0.2–0.4) at 25 °C. Here, a novel polymer matrix of SPEs that simultaneously promotes lithium salt dissociation and ion transportation based on a high dielectric poly(vinylidene fluoride‐trifluoroethylene‐chlorotrifluoroethylene) (TerP) and an all‐trans conformational poly(vinylidene fluoride‐trifluoroethylene) (CoP), is developed. The high dielectric constant increases the polarity of CH2CF2 polar groups; then, brings a strong electronegative end that dissociates Li+ from lithium salts. The all‐trans conformation assures all fluorine atoms locate on one side of the chain, constructing ion hopping highways. As a result, the TerP/CoP (TC) SPE exhibits a high ionic conductivity (2.37 × 10−4 S cm−1) and a quite large tLi+ of 0.61 at 25 °C. The Li/TC SPE/Li symmetric cells cycle stably for more than half a year (>4500 h) and the LiNi0.8Co0.1Mn0.1O2/TC SPE/Li cell cycles steadily for 1000 and 600 cycles at 1 C and 2 C at 25 °C, respectively. This work paves a new way to prepare high‐performance SPEs by simultaneously modulating dielectric constants and conformation of polymers.
Through conformational regulation of the high dielectric P(VDF‐TrFE‐CTFE), an all‐trans conformation with all F atoms located on one side of the chain is achieved, which constructs ion hopping highways and results in a high lithium‐ion transference number of 0.61. Both the Li//Li symmetric cells and the high‐voltage NCM811//Li cells show long‐term cycling stability at 25 °C.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The substitution of petroleum-based self-healing elastomers with biobased counterparts is crucial to the global sustainable development of the rubber industry, which highly depends on the ease of the ...synthesis procedure. Herein, we show that highly stretchable, recyclable, and self-healable biobased elastomers were synthesized via condensation polymerization of succinic acid, adipic acid, sebacic acid, and 1,4-butanediol in the presence of a small amount of glycerol as a curing agent and 3,3′-dithiodipropionic acid as a dynamic covalent monomer. The macroscopic properties of our elastomers, including thermal, mechanical, stress relaxation, and self-healing performance, were finely regulated via microscopic chemical and topological structure. As such, a highly stretchable (up to ∼1700%), recyclable (almost without degradation of the mechanical performance over several repeats), rapid room temperature self-healable (in 20 min) biobased vitrimeric elastomer was achieved, which is the first aliphatic disulfide metathesis assisted self-healing polymer achieved at such low temperatures. The ease of the polycondensation with which the elastomers can be readily scaled up points to exciting opportunities for sustainable polymers with minimal environmental impact.
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IJS, KILJ, NUK, PNG, UL, UM
•Atrial fibrillation (AF) is a serious cardiac condition among patients with cardiovascular diseases.•MicroRNAs are significantly related to the underlying mechanism of AF.•Circulating microRNAs may ...be the more suitable biomarker for early diagnosis of AF.
Atrial fibrillation (AF) causes severe cardiac dysrhythmia among patients with cardiovascular diseases. AF increases the risk of stroke and heart failure and is a growing public health concern. AF is also associated with various disease conditions such as hypertension, coronary artery disease, aging, and diabetes mellitus. The mechanism underlying AF is not completely understood due to its complexity. However, experimental and clinical data have revealed that the prevalence of this disease is associated with atrial arrhythmogenic remodeling. Currently, there are no biomarkers that are available for the early diagnosis of AF. Several studies have proposed microRNAs (miRNAs) as useful biomarkers for the diagnosis of AF due to their stability and easy availability both in atrial tissue and circulating blood. miRNAs play an important role in the development of the heart. The dysregulation of miRNA expression is associated with cardiac remodeling. Genetic factors strongly contribute to the pathogenesis of AF. Recently, single nucleotide polymorphisms (SNPs) in various genes and miRNAs have been reported to be associated with AF. The aim of this review was to discuss the correlation between SNPs in miRNAs and AF, including those miRNAs that are commonly reported as potential biomarkers for AF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms ...of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloids (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds.
Background and Aims
NAFLD is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance, obesity and hyperlipidemia. NASH is a progressive stage of NAFLD ...with severe hepatic steatosis, hepatocyte death, inflammation, and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases, regulates many metabolism‐associated signaling pathways. However, the role of OTUB1 in NASH is unclarified.
Methods and Results
We demonstrated that mice with Otub1 deficiency exhibited aggravated high‐fat diet–induced and high‐fat high‐cholesterol (HFHC) diet–induced hyperinsulinemia and liver steatosis. Notably, hepatocyte‐specific overexpression of Otub1 markedly alleviated HFHC diet–induced hepatic steatosis, inflammatory responses, and liver fibrosis. Mechanistically, we identified apoptosis signal–regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA‐sequencing analysis and immunoblot analysis. Through immunoprecipitation–mass spectrometry analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor–associated factor 6 (TRAF6) and suppressed its lysine 63–linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway.
Conclusions
OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6‐mediated ASK1 activation. Targeting the OTUB1‐TRAF6‐ASK1 axis may be a promising therapeutic strategy for NASH.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent ...target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12‐deficient mice exhibit high‐fat diet (HFD)–induced and high‐fat high‐cholesterol diet–induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD‐induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal‐regulating kinase 1 (ASK1), which mediates the mitogen‐activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1‐related proteins, JUN N‐terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high‐fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the genus Macleaya, Macleaya cordata and Macleaya microcarpa have been recognized as traditional herbs that are primarily distributed in China, North America, and Europe and have a long history of ...medicinal usage. These herbs have been long valued and studied for detumescence, detoxification, and insecticidal effect. This review aims to provide comprehensive information on botanical, phytochemical, pharmacological, and toxicological studies on plants in the genus Macleaya. Plants from the genus of Macleaya provide a source of bioactive compounds, primarily alkaloids, with remarkable diversity and complex architectures, thereby having attracted attention from researchers. To date, 291 constituents have been identified and/or isolated from this group. These purified compounds and/or crude extract possess antitumor, anti‐inflammatory, insecticidal, and antibacterial activities in addition to certain potential toxicities. Macleaya species hold potential for medicinal applications. However, despite the pharmacological studies on these plants, the mechanisms underlying the biological activities of active ingredients derived from Macleaya have not been thoroughly elucidated to date. Additionally, there is a need for research focusing on in vivo medical effects of Macleaya compounds and, eventually, for clinical trials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Spring tide amplifies more than neap tide in Qiantang Estuary.•Tidal dynamics is strongly influenced by morphological evolution.•A conceptual model of river-tide-morphology interaction is proposed.
...Understanding tidal dynamics in estuaries is essential for tidal predictions and assessments of sediment transport and associated morphological changes. Most studies on river-tide interaction ignored the influences of morphological evolutions under natural conditions such as the seasonal and interannual variations of river discharge. This study analyzes the multiple-timescale tidal dynamics in the Qiantang Estuary, a macro-tidal estuary in China with an extremely active morphological evolution. A large dataset including water levels at representative stations, river discharges and bathymetries since 1980 has been collected. The results of the analysis show that within a spring-neap cycle, the tidal amplification in the upper estuary is stronger during spring tide than during neap tide. This unexpected behavior is due to the high sediment concentration and the unique longitudinal profile of the estuary. On the seasonal and interannual timescales, the low water levels in the upper estuary depend on the local bathymetrical conditions. Tidal ranges in the upper estuary are larger in the high flow season and years, than in the low flow season and years, due to the erosion at high flow, in contrast to estuaries with less active morphological changes. During low flow season and years, the bed is gradually recovered, the low waters are elevated, and the tidal ranges decrease accordingly. A good relationship exists between the tidal ranges and the depth of the upper estuary. In the lower estuary, the flood dominance increases continuously due to embankment. In the upper estuary, the flood dominance is increased during the high flow periods, explaining the fast sediment input and bed recovery in the post high flow periods. A conceptual model of river-tide-morphology interaction of the estuary is proposed, which is also applicable for other shallow systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cohort studies have linked metabolic syndrome (MetS) to gastrointestinal (GI) cancer risk. We aimed to evaluate the associations between MetS, its components, and combinations of MetS components with ...eight GI cancers risk.
We conducted a systematic search of prospective cohort studies and performed a meta-analysis. Subgroup analyses regarding diagnostic criteria, sex, cancer sites, histological subtypes, ethnic groups, and studies adjusted for alcohol consumption were carried out. Mendelian randomization (MR) was employed to evaluate the causality between 17 MetS-related traits and eight GI cancers among Europeans and Asians separately.
Meta-analyses of 31 prospective studies indicated that MetS was significantly associated with an increased risk of colorectal cancer (CRC) (RR 95% CI = 1.13 1.12-1.15), esophageal cancer (EC) (RR 95% CI = 1.17 1.03-1.32), gallbladder cancer (GBC) (RR 95% CI = 1.371.10-1.71), liver cancer (LC) (RR 95% CI = 1.46 1.29-1.64), and pancreatic cancer (PaC) (RR 95% CI = 1.25 1.20-1.30), but not gastric cancer (GC) (RR 95% CI = 1.11 0.96-1.28). Regarding the associations between MetS components and GI cancers risk, the following associations showed statistical significance: obesity-CRC/LC/EC/, hypertriglyceridemia-LC/PaC, reduced high-density lipoprotein (HDL)-CRC/LC/GC/PaC, hyperglycemia-CRC/LC/PaC, and hypertension-CRC/LC/EC/PaC. Sex-specific associations were observed between individual MetS components on GI cancers risk. Among the top three common combinations in both sexes, obesity + HTN + hyperglycemia had the strongest association with CRC risk (RR 95% CI = 1.54 1.49-1.61 for males and 1.27 1.21-1.33 for females). MR analyses revealed causality in 16 exposure-outcome pairs: waist-to-hip ratio/BMI/HbA1c-CRC; BMI/childhood obesity/waist circumference/T2DM/glucose-EC; BMI/waist circumference/cholesterol-LC; cholesterol/childhood obesity/waist circumference/HbA1c-PaC; and HbA1c-GBC. These results were robust against sensitivity analyses.
Since MetS is reversible, lifestyle changes or medical interventions targeting MetS patients might be potential prevention strategies for GI cancers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and ...immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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