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Centromere protein A (CENP‐A), a centromere‐specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure‐activity relationship (SAR) study of the cell‐cycle‐arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)‐6‐Br‐JP18 and (+)‐6‐Cl‐JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X‐ray crystallography analysis reveals that both molecules bind to the colchicine‐binding site of β‐tubulin. Treatment of human cells with microtubule‐targeting agents (MTAs), including these two compounds, results in CENP‐A accumulation by destabilizing Cdh1, a co‐activator of the anaphase‐promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP‐A accumulation using small‐molecule tools and highlights the role of Cdh1 in CENP‐A proteolysis. [ABSTRACT FROM AUTHOR]

Background: Postoperative sleep disorder (PSD) and delirium, which may be associated with surgery and inhalational anesthetics, induce adverse effects in old adults. Emerging evidence indicates that circadian rhythm contributes to various neuropathological diseases, including Alzheimer's disease. Thus, we analyzed the potential role of circadian rhythm in PSD and delirium‐like behavior in aged mice and determined whether exogenous melatonin could facilitate entrainment of the circadian rhythm after laparotomy under sevoflurane anesthesia. Methods: We selected old C57BL/6J mice which receiving laparotomy/sevoflurane anesthesia as model animals. We employed buried food, open field, and Y maze test to assess delirium‐like behavior, and electroencephalography/electromyography (EEG/EMG) were used to investigate sleep changes. We analyzed the transcription rhythm of clock genes in superchiasmatic nucleus (SCN) to explore the effects of surgery and melatonin pretreatment on the circadian rhythm. Then, we measured melatonin receptor levels in SCN and ERK/CREB pathway‐related proteins in hippocampus and prefrontal cortex to assess their role in PSDs and delirium‐like behavior. Results: Laparotomy under sevoflurane anesthesia had a greater influence than sevoflurane alone, leading to sleep disorder, a shift in sleep–wake rhythm, and delirium‐like behavior. Bmal1, Clock, and Cry1 mRNA expression showed a peak shift, MT1 melatonin receptor expression level was increased in the SCN, and p‐ERK/ERK and p‐CREB/CREB were decreased in hippocampus and prefrontal cortex of aged mice 1 day after laparotomy. Melatonin showed significant efficacy in ameliorating PSD and delirium‐like behavior and restoring the circadian rhythm, reversing melatonin receptor and ERK/CREB pathway expression abnormalities. In addition, most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist. Conclusions: Melatonin receptors in SCN, circadian rhythm, and ERK/CREB signaling pathway participate in the pathophysiological processes of PSD and delirium‐like behavior. Melatonin intervention could be a potential preventative approach for PSD and delirium. [ABSTRACT FROM AUTHOR]

A technique combining ion mobility spectrometry‐mass spectrometry (IMS‐MS) and supercharging electrospray ionization (ESI) has been demonstrated to differentiate protein chemical topology effectively. Incorporating as many charges as possible into proteins via supercharging ESI allows the protein chains to be largely unfolded and stretched, revealing their hidden chemical topology. Different chemical topologies result in differing geometrical sizes of the unfolded proteins due to constraints in torsional rotations in cyclic domains. By introducing new topological indices, such as the chain‐length‐normalized collision cross‐section (CCS) and the maximum charge state (zM) in the extensively unfolded state, we were able to successfully differentiate various protein chemical topologies, including linear chains, ring‐containing topologies (lasso, tadpole, multicyclics, etc.), and mechanically interlocked rings, like catenanes. [ABSTRACT FROM AUTHOR]

Background: Reactive stroma is recognized as one of the independent prognostic factors in prostate cancer (PCa). Intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) may be useful for assessing the reactive stromal grade (RSG).Purpose: To investigate whether IVIM and DKI models can evaluate RSG in PCa patients.Study Type: Retrospective.Subjects: A total of 56 PCa patients aged 73 years on average confirmed by MRI and transrectal ultrasound (MRI/TRUS) fusion biopsy divided into two subgroups (18 high RSG and 38 low RSG).Field Strength/sequence: A 3 T/T1 WI-fs, T1 WI, T2 WI-fs, T2 WI, DWI, IVIM, and DKI.Assessment: Apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusion (MD), mean kurtosis (MK) were obtained. Patients were divided into high RSG PCa (>50% reactive stroma) and low RSG PCa (≤50% reactive stroma) groups on hematoxylin and eosin (H&E) stained sections.Statistical Tests: Spearman correlation and independent sample t-test or Wilcoxon's rank sum test was used to investigate the relationship between each imaging parameter and RSG. The combined parameters were calculated using a binary logistic regression model. Receiver operating characteristic (ROC) analysis was used to explore the value of individual and combined parameters to differentiate between high and low RSG group. Area under the ROC curves (AUC) > 0.7 were used as reference standards.Results: ADC, D, f, and MD values showed positive correlation with RSG (r = 0.489, 0.619, 0.318, and 0.544, respectively); MK showed negative correlation with RSG (r = -0.444). ADC, D, f, and MD values were significantly lower in the low RSG group than in the high RSG group. The combined model showed the best diagnostic ability to differentiate low and high RSG groups (AUC = 0.887).Data Conclusion: Parameters of IVIM and DKI may be promising methods for assessment of RSG in PCa patients.Evidence Level: 3.Technical Efficacy: Stage 3. [ABSTRACT FROM AUTHOR]

DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs, but clinical efficacy is often compromised due to chemoresistance. In this study, we investigate the role of TOP2A O‐GlcNAcylation in breast cancer cells and patient tumor tissues. Our results demonstrate that elevated TOP2A, especially its O‐GlcNAcylation, promotes breast cancer malignant progression and resistance to adriamycin (Adm). O‐GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models. Mechanistically, O‐GlcNAcylation‐modulated interactions between TOP2A and cell cycle regulators influence downstream gene expression and contribute to breast cancer drug resistance. These results reveal a previously unrecognized mechanistic role for TOP2A O‐GlcNAcylation in breast cancer chemotherapy resistance and provide support for targeting TOP2A O‐GlcNAcylation in cancer therapy. Synopsis: O‐GlcNAcylation at Ser1469 enhances chromatin binding and catalytic activity of TOP2A. O‐GlcNAcylation also enhances the interaction between TOP2A and cell cycle regulators, thereby playing a crucial role in breast cancer progression and Adm resistance. TOP2A can be O‐GlcNAcylated by OGT at Ser1469 in vitro and in vivo.O‐GlcNAcylation promotes TOP2A chromatin binding.TOP2A O‐GlcNAcylation elevates its DNA cleavage and decatenation activity.O‐GlcNAcylation of TOP2A drives breast cancer progression and drug resistance. [ABSTRACT FROM AUTHOR]

Practical implementation of alkali metal batteries currently still faces formidable challenges because of the dendrite growth upon continuous charge/discharge processes and the associated unstable solid–electrolyte interphase. Herein, it is reported that dendrites can be fundamentally mitigated in lithium and sodium metal batteries by regulating the Li+ and Na+ flux using a glass fiber (GF) separator impregnated with polytetrafluoroethylene nanospheres (PTFE‐NSs), which results in homogeneous deposition of Li and Na during charging. The COMSOL Multiphysics simulations reveal that the introduction of negatively charged PTFE‐NSs into the GF separator enhances the local electric field near the anode, thereby boosting the transfer of cations. It is demonstrated that Li//Li and Na//Na symmetric cells utilising a PTFE‐GF separator show outstanding cycle stability of 1245 and 2750 h, respectively, at 0.5 mA cm−2. Moreover, the Li//LiFePO4 and Na//Na3V2(PO4)2F3 full cells exhibit remarkably improved capacity retention when cycled at 1 C, in the presence of a PTFE‐GF separator. The nuclear magnetic resonance spectroscopy studies suggest that the impregnation of PTFE‐NSs into GF helps "liberate" more Li+ and Na+ and changes the coordination interaction between ions and solvents, contributing to the enhanced electrochemical performance. [ABSTRACT FROM AUTHOR]

Background: Diffusion‐weighted imaging (DWI) has demonstrated great potential in predicting the expression of tumor cell proliferation and apoptosis indexes. Purpose: To evaluate the impact of four region of interest (ROI) methods on interobserver variability and apparent diffusion coefficient (ADC) values and to examine the correlation of ADC values with Ki‐67, Bcl‐2, and P53 labeling indexes (LIs) in a murine model of fibrosarcoma. Study Type: Prospective, animal model. Animal Model: A total of 22 female BALB/c mice bearing intramuscular fibrosarcoma xenografts. Field Strength/Sequence: A 3.0 T/T1‐weighted fast spin‐echo (FSE), T2‐weighted fast relaxation fast spin‐echo, and DWI PROPELLER FSE sequences. Assessment: Four radiologists measured ADC values using four ROI methods (oval, freehand, small‐sample, and whole‐volume). Immunohistochemical assessment of Ki‐67, Bcl‐2, and P53 LIs was performed. Statistical Tests: Interclass correlation coefficient (ICC), one‐way analysis of variance followed by LSD‐t post hoc analysis, and Pearson correlation test were performed. The statistical threshold was defined as a P‐value of <0.05. Results: All ROI methods for ADC measurements showed excellent interobserver agreement (ICC range, 0.832–0.986). The ADC values demonstrated significant differences among the four ROI methods. The ADC values for oval, freehand, small‐sample, and whole‐volume ROI methods showed a moderately negative correlation with Ki‐67 (r = −0.623; r = −0.629; r = −0.642, and r = −0.431) and Bcl‐2 (r = −0.590; r = −0.597; r = −0.659, and r = −0.425) LIs, but no correlation with P53 LI (r = 0.364, P = 0.104; r = 0.350, P = 0.120; r = 0.379, P = 0.091; r = 0.390, P = 0.080). Data Conclusion: The ADC value can be used to evaluate cell proliferation and apoptosis indexes in a murine model of fibrosarcoma, employing the small‐sample ROI as a reliable method. Evidence Level: 1 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between DWI, intravoxel incoherent motion (IVIM), and hypoxia‐inducible factor 1‐alpha (HIF‐1α) expression in a nude mouse model of rhabdomyosarcoma based on imaging and pathological comparisons. Methods: Human rhabdomyosarcoma‐derived (RD) cells were inoculated into the right thigh muscle of 20 BALB/c female nude mice. Mice were imaged using 3.0 Tesla MRI system. T1‐weighted imaging, T2‐weighted imaging, DWI, and IVIM images were obtained. ADW4.7 (GE Healthcare, ChicagoAQ34, IL, USA) was used for image processing of ADC, Dslow, Dfast, and f values. All parameter values were independently analyzed by 2 observers. Immunohistochemistry of HIF‐1α was performed. We used a specific image–pathology comparison method to ensure correct overlap between the image plane and the pathological section. Mann–Whitney U test or independent sample t test, Pearson or Spearman correlation test, the intragroup correlation coefficient, Kolmogorov–Smirnov test, and receiver operating characteristic curve were used. The correlation between DWI and intravoxel incoherent motion parameter values and HIF‐1α expression was determined. Results: There were 10 mice in the low‐expression group and 7 in the high‐expression group. The ADC and Dslow values were negatively correlated with HIF‐1α with correlation coefficients of −0.491 and − 0.702 (P = 0.045 and 0.002). The f value positively correlated with HIF‐1α expression (r = 0.485, P = 0.048). ADC, Dslow, and f were significantly different between the high‐HIF‐1α expression tumors and the low‐HIF‐1α expression tumors. ADC showed the best predictive performance among all parameters (area under the curve = 0.652, sensitivity = 83.3%, specificity = 63.6%). Conclusion: The parameter values of DWI and intravoxel incoherent motion can be used to evaluate the expression of HIF‐1α in rhabdomyosarcoma. ADC, Dslow, and f value showed correlation with the expression of HIF‐1α. [ABSTRACT FROM AUTHOR]

Over the past two decades, considerable efforts have been made to develop non‐invasive methods for determining tumor grade or surrogates for predicting the biological behavior, aiding early treatment decisions, and providing prognostic information. The development of new imaging tools, such as diffusion‐weighted imaging, diffusion kurtosis imaging, perfusion imaging, and magnetic resonance spectroscopy have provided leverage in the diagnosis of soft tissue sarcomas. Artificial intelligence is a new technology used to study and simulate human thinking and abilities, which can extract and analyze advanced and quantitative image features from medical images with high throughput for an in‐depth characterization of the spatial heterogeneity of tumor tissues. This article reviews the current imaging modalities used to predict the histopathological grade of soft tissue sarcomas and highlights the advantages and limitations of each modality. Level of Evidence: 5 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: High cellularity and abnormal interstitial structures are some of the unfavorable factors that affect the treatment outcomes and survival of rhabdomyosarcoma (RMS) patients. Purpose To explore the correlation between diffusion‐weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with quantitative histopathologic features in a murine model of RMS. Study Type: Prospective. Animal Model: Murine model of RMS (31 female BALB/c nude mice). Field Strength/Sequence: 3.0 T; fast spin‐echo (FSE) T1‐weighted imaging, fast relaxation fast spin‐echo (FRFSE) T2‐weighted imaging, DWI PROPELLER FSE imaging sequence, and IVIM echo planar imaging sequence; 10 different b‐values (0, 50, 100, 150, 200, 400, 600, 800, 1000, and 1200 s/mm2). Assessment Magnetic resonance imaging (MRI) was performed after 30–45 days of implantation. The following MRI parameters were calculated: apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo‐diffusion coefficient (D*), and perfusion fraction (f). Histopathologic features, which contained nuclear, cytoplasmic, and stromal fractions, and the nuclear‐to‐cytoplasmic ratio within the tumor were measured using image‐based segmentation. Statistical Tests: Pearson's correlation, multiple linear regression analysis, and receiver operating characteristic curve analysis were performed. A P < 0.05 was considered statistically significant. Results: The ADC value showed moderate negative correlation with nuclear fraction (r = −0.540), and moderate positive correlation with stroma fraction (r = 0.474). The D value showed moderate negative correlation with nuclear fraction (r = −0.491), and moderate positive correlation with stroma fraction (r = 0.421). The f value showed a moderate negative correlation with stroma fraction (r = −0.423). The D value showed the best diagnostic ability. The optimal cut‐off D value of 0.460 was associated with 77.8% sensitivity and 68.2% specificity (area under the curve, 0.747). Data Conclusion: The ADC, D, and f values obtained from DWI and IVIM images showed moderate correlation with the quantitative histopathologic features in a murine model of RMS. Level of Evidence: 1 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

Summary: Leucine‐rich repeat‐receptor‐like kinase (LRR‐RLK) is a large subfamily of plant RLKs; however, its role in cold tolerance is still unknown. A novel cold tolerance LRR‐RLK gene (MtCTLK1) in Medicago truncatula was identified using the transgenic lines overexpressing MtCTLK1 (MtCTLK1‐OE) and mtctlk1 lines with Tnt1 retrotransposon insertion. Compared with the wild‐type, MtCTLK1‐OE lines had increased cold tolerance and mtctlk1 showed decreased cold tolerance. The impaired cold tolerance in mtctlk1 could be complemented by the transgenic expression of MtCTLK1 or its homolog MfCTLK1 from Medicago falcata. Antioxidant enzyme activities and proline accumulation as well as transcript levels of the associated genes were increased in response to cold, with higher levels in MtCTLK1‐OE or lower levels in mtctlk1 lines as compared with wild type. C‐Repeat‐Binding Factors (CBFs) and CBF‐dependent cold‐responsive genes were also induced in response to cold, and higher transcript levels of CBFs and CBF‐dependent cold‐responsive genes were observed in MtCTLK1‐OE lines whereas lower levels in mtctlk1 mutants. The results validate the role of MtCTLK1 or MfCTLK1 in the regulation of cold tolerance through the CBF pathway, antioxidant defense system and proline accumulation. It also provides a valuable gene for the molecular breeding program to improve cold tolerance in crops. Significance Statement: A novel cold tolerance leucine‐rich repeat‐receptor‐like kinase was identified from Medicago truncatula. It confers cold tolerance through regulation on the C‐repeat‐binding factor cold response pathway, antioxidant defense, and proline accumulation. [ABSTRACT FROM AUTHOR]

Many studies have shown, using two‐dimensional culture, that low‐temperature plasma‐jet‐activated medium (PAM) inhibits the growth of various tumor cells, whereas its effects and mechanisms in the three‐dimensional (3D) culture system remain unclear. In this study, a 3D cell culture model was used to study the inhibition of tumorigenesis of PAM in vitro. Our results showed that PAM significantly suppressed tumor spheroid formation and downregulated stemness‐related genes of A549 cells "before," "during," and "after" sphere formation. Additionally, we found that the specific signature of reactive oxygen species‐induced autophagy was involved in the antiproliferation effect of PAM on A549 spheroids. Our study complemented and extended the application of PAM for its anticancer effects in lung adenocarcinoma cancer. [ABSTRACT FROM AUTHOR]

Rechargeable potassium metal batteries are promising energy storage devices with potentially high energy density and markedly low cost. However, eliminating dendrite growth and achieving a stable electrode/electrolyte interface are the key challenges to tackle. Herein, a novel "quasi‐liquid" potassium‐sodium alloy (KNA) anode comprising only 3.5 wt% sodium (KNA‐3.5) is reported, which exhibits outstanding electrochemical performance able to be reversibly cycled at 4 mA cm–2 for 2000 h. Moreover, it is demonstrated that adding a small amount of sodium hexafluorophosphate (NaPF6) into the potassium bis(fluorosulfonyl)imide electrolyte allows for the formation of the "quasi‐liquid" KNA on electrode surface. Comprehensive experimental studies reveal the formation of an unusual metastable KNa2 phase during plating, which is believed to facilitate simultaneous nucleation and suppress the growth of dendrites, thereby improving the electrode's cycle lifetime. The "quasi‐liquid" KNA‐3.5 anode demonstrates markedly enhanced electrochemical performance in a full cell when pairing with Prussian blue analogs or sodium rhodizonate dibasic as the cathode material, compared to the pristine potassium anode. Importantly, unlike the liquid KNA reported before, the "quasi‐liquid" KNA‐3.5 exhibits good processability and can be readily shaped into sheet electrodes, showing substantial promise as a dendrite‐free anode in rechargeable potassium metal batteries. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to determine the effects of sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) in heart failure with reduced ejection fraction (HFrEF), compare the effect of SGLT2i with angiotensin receptor neprilysin inhibitor (ARNI), and find whether combination of SGLT2i and ARNI is better than monotherapy. Methods and results: Embase, Medline, and Cochrane Central Registry of Controlled Trials were searched for randomized controlled trials evaluating SGLT2i or ARNI in HFrEF. And a total of six trials were included. SGLT2i was found to significantly reduce the risk of cardiovascular death or hospitalization for heart failure by 27% [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.67–0.80], hospitalization for heart failure by 31% (HR 0.69, 95% CI 0.62–0.77), cardiovascular death by 16% (HR 0.84, 95% CI 0.74–0.95), and all‐cause death by 16% (HR 0.84, 95% CI 0.75–0.94) in HFrEF only with a statistically higher risk of genital infection (risk ratio (RR) 2.78, 95% CI 1.46–5.29). The reduction in cardiovascular death or hospitalization for heart failure was of similar magnitude in patients with or without diabetes mellitus (HR 0.71, 95% CI 0.64–0.80 vs. HR 0.75, 95% CI 0.65–0.87) using SGLT2i. Indirect treatment comparison showed that SGLT2i and ARNI had similar effects on primary outcome (HR 0.93, 95% CI 0.82–1.06). And combination of SGLT2i and ARNI achieved a better prognosis performance (HR 0.68, 95% CI 0.53–0.89) compared with ARNI monotherapy. Conclusions: SGLT2i could safely reduce cardiovascular death or hospitalization for heart failure in HFrEF regardless of diabetes mellitus status. SGLT2i and ARNI demonstrate similar effects, while combination of SGLT2i and ARNI results in a better cardiovascular protective effect. [ABSTRACT FROM AUTHOR]

Although graphene has been developed and widely used in many fields over the past decades, the effect of oxygen (O2) on the exfoliation of graphite is still unclear. Here, a simple bubble‐triggered exfoliation method is employed for controllable synthesis of graphene nanoplatelets (GNPs) with low‐oxidation level and high electrical conductivity. The exfoliation process is studied and a formation mechanism for the synthesis of the low‐defect GNPs is proposed. The results show that the synergistic effect of H2SO4 and H2O2 plays an important role in the procession of exfoliation of graphite. Moreover, density functional theory (DFT) simulations exhibit that H2O2 would preferentially adsorb on the edge of graphite, indicating the possibility to initiate the exfoliation by O2. In the whole process, some oxygen free radicals can be released from H2O2, resulting in some O2 and oxygen functional groups formed on the graphite edge, and which can finally lead to the fast exfoliation of graphite. In addition, a time‐dependent temperature profile under an applied voltage of 5 V exhibits a steady‐state with temperature up to 275 °C. Overall, this work elucidates the selectivity of gas bubble absorbed on the side edge of graphite and presents a potential application for high‐electrical conductivity graphene. [ABSTRACT FROM AUTHOR]

Common vetch (Vicia sativa L.) is a leguminous plant used as forage and cover crops. A protocol of ethyl methanesulfonate (EMS)‐induced mutations was established in the present study, based on analysis of seed germination and emergence rate, seedling growth and abnormal plant percentage as affected by combinations of EMS concentration and treatment time. Treatment of seeds with 0.1% EMS for 9 and 12 hr or 0.5% EMS for 6 and 9 hr led to 43%–66% normal plants, which was suggested to be used for EMS‐induced mutations in common vetch. The wild‐type common vetch showed red with accumulation of anthocyanins in winter, and two lines showing separation of anthocyanin accumulation (labeled as A+) and without anthocyanin accumulation (labeled as A–) plants were selected from M2 plants induced by EMS in the field. The A– plants showing green color had higher plant height and fresh shoot weight than the A+ plants during wintering, with lower ion leakage after freezing treatment, indicating that the green mutants (A–) had increased cold tolerance. Compared to A+ plants, the green mutants had significantly increased ascorbate (AsA) level in response to low temperature treatment. The results suggest that the increased AsA level under low temperature was associated with the increased cold tolerance in the green mutants. [ABSTRACT FROM AUTHOR]

Soft magnetic micro/nanostructures are highly desirable for pursuing excellent magnetic properties and electromagnetic wave (EMW) absorption performance. However, their magnetic loss at high frequency is usually very low due to the sharp drop of permeability, and thus results in a heavy loading in matrix and a large layer thickness, which are not conductive to the development of ultralight and ultrathin EMW absorbers. Here, an ultralight and ultrathin EMW absorber based on a parallel Ni wire array are reported, and an orientation‐enhanced strategy to improve EMW absorption performance is proposed. Combining with the finite element simulation, it is found that the parallel orientation of Ni wires with a capacitor‐like structure enhances the interfacial polarization, thereby improving dielectric loss. The strong shape anisotropy caused by orientation increases magnetic loss by enhancing magnetic resonances, which further improves impedance matching. The parallel Ni wire array exhibits excellent EMW absorption and achieves the largest specific reflection loss (reflection loss/(thickness × loading)) among magnetic wire‐based absorbers. [ABSTRACT FROM AUTHOR]

Post‐operative sleep disorders induce adverse effects on patients, especially the elderly, which may be associated with surgery and inhalational anaesthetics. Melatonin is a neuroendocrine regulator of the sleep‐wake cycle. In this study, we analysed the alterations of post‐operative sleep in aged melatonin‐deficient (C57BL/6J) mice, and investigated if exogenous melatonin could facilitate entrainment of circadian rhythm after laparotomy under sevoflurane anaesthesia. The results showed that laparotomy under sevoflurane anaesthesia had a greater influence on post‐operative sleep than sevoflurane alone. Laparotomy under anaesthesia led to circadian rhythm shifting forward, altered EEG power density and delta power of NREM sleep, and lengthened REM and NREM sleep latencies. In the light phase, the number of waking episodes tended to decline, and wake episode duration elevated. However, these indicators presented the opposite tendency during the dark phase. Melatonin showed significant efficacy for ameliorating the sleep disorder and restoring physiological sleep, and most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist. [ABSTRACT FROM AUTHOR]

Cooperative microgrids (CMGs) can effectively solve the energy interaction between microgrids (MGs) while increasing the penetration rate of renewable energy systems (RESs) and reducing the interaction frequency with the grid. However, the uncertainty of RESs will bring new challenges to the energy management and economic dispatch of CMGs, especially in increasing the number of MGs connected to the grid. Taking into account this uncertainty, it is extremely unlikely that the forecast uncertainty information will be at the worst values in every period, and this forecast uncertainty information is near the expected values in most cases. Therefore, a two-stage robust optimal model under expected scenarios for CMGs is proposed in this study to improve the conservatism of traditional models and minimise the daily cost. In this model, the first-stage decision results (FDRs) are determined by minimising the daily cost of CMGs under the expected scenarios. The proposed model is transformed based on two-stage zero-sum game theory and dual theory, a column and constraint generation algorithm is first used to test the robust feasibility of the FDR, and the second-stage decision results can be obtained without changing the FDR. Case studies verify that the proposed model can effectively solve energy transactions between MGs while mitigating the uncertainty disturbances in the operation of CMGs. [ABSTRACT FROM AUTHOR]

Entangled proteins have attracted significant research interest. Herein, we report the first rationally designed lasso proteins, or protein [1]rotaxanes, by using a p53dim‐entwined dimer for intramolecular entanglement and a SpyTag‐SpyCatcher reaction for side‐chain ring closure. The lasso structures were confirmed by proteolytic digestion, mutation, NMR spectrometry, and controlled ligation. Their dynamic properties were probed by experiments such as end‐capping, proteolytic digestion, and heating/cooling. As a versatile topological intermediate, a lasso protein could be converted to a rotaxane, a heterocatenane, and a "slide‐ring" network. Being entirely genetically encoded, this robust and modular lasso‐protein motif is a valuable addition to the topological protein repertoire and a promising candidate for protein‐based biomaterials. [ABSTRACT FROM AUTHOR]

Herein, we report the biosynthesis of protein heterocatenanes using a programmed sequence of multiple post‐translational processing events including intramolecular chain entanglement, in situ backbone cleavage, and spontaneous cyclization. The approach is general, autonomous, and can obviate the need for any additional enzymes. The catenane topology was convincingly proven using a combination of SDS‐PAGE, LC‐MS, size exclusion chromatography, controlled proteolytic digestion, and protein crystallography. The X‐ray crystal structure clearly shows two mechanically interlocked protein rings with intact folded domains. It opens new avenues in the nascent field of protein‐topology engineering. [ABSTRACT FROM AUTHOR]

Ground walking in humans is typically stable, symmetrical, characterized by smooth heel‐to‐toe ground contact. Previous studies on children with autism spectrum disorder (ASD) identified various gait abnormalities. However, they produced inconsistent findings, particularly for the occurrence of toe walking and gait symmetry between feet, owing to their reliance on retrospective reports, visual analysis of videos, or kinematic analysis of the gait. The present study examined gait functions in children with ASD using plantar pressure that quantified foot–ground interaction with high spatial and temporal resolutions. Fifty‐eight 4–6‐year‐old children with ASD (12 low‐functioning and 46 high‐functioning autism) and 28 age‐matched typically developed children walked straight 6 m at their preferred speed for 10 repetitions. We found that both ASD groups walked with more flat‐footed contact pattern, more left–right asymmetry, and larger step‐to‐step variability than their controls. Furthermore, these abnormal gait characteristics were related to social impairments measured by the Autism Spectrum Quotient and Social Responsive Scale, supporting a close association between impaired motor coordination and core symptoms of autism. Autism Res 2020, 13: 1215‐1226. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We examined gait functions among children with autism by measuring their foot plantar pressure during simple straight walking. Children with ASD walked with a characteristic foot‐ground contact pattern with inappropriate contact forces and large step‐to‐step variability when compared with their age‐matched controls. These walking abnormalities were dependent on their social impairments but independent from their intelligence, indicating a close relationship between atypical motor coordination and core symptoms of autism. [ABSTRACT FROM AUTHOR]

Background: Apelin plays an important role in many types of tumors. We aimed to identify the effects of miR‐195 on inhibiting apelin and clarify the regulating mechanism of miR‐195‐apelin in lung adenocarcinoma cells. Methods: We detected the expression levels of apelin and miR‐195 in lung adenocarcinoma tissues and lung cancer cell lines using Western blotting and quantitative reverse transcription PCR assay, respectively. Luciferase reporter assay was used to confirm the target gene of miR‐195. The effects of miR‐195 and apelin on the proliferation and cell cycle of lung adenocarcinoma cells were assessed by methyl thiazolyl tetrazolium and colony formation assays, and flow cytometry. Wound‐healing and transwell invasion experiments were employed to examine cellular migration and invasion. A tumor xenograft model was then used to investigate the role of miR‐195 on tumor growth in vivo. Results: The expression level of apelin and miR‐195 showed an inverse correlation in lung adenocarcinoma tissues and cell lines. Luciferase reporter assay suggested that miR‐195 directly targets apelin messenger RNA. Overexpression of miR‐195 significantly inhibited the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and suppressed tumor growth in vivo. Further analysis revealed that apelin is one of the functional target genes of miR‐195, and the overexpression of apelin efficiently inhibits the promotion of cell proliferation and invasion mediated by miR‐195 mimics in lung adenocarcinoma cells. Conclusions: Our data constitute evidence that miR‐195 inhibits lung adenocarcinoma cell proliferation and invasion though targeting apelin and provides novel insight into the mechanism underlying the development of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Copper metal catalysts suffer from gradual loss of activity due to the agglomeration and sintering of active metals during the catalytic reaction processes. Herein, we show that enhanced catalytic durability for methanol steam reforming (MSR) can be achieved by using Ni modified Cu−Al spinel solid solution as catalysts without pre‐reduction treatment. In so doing, Cu atoms can be gradually released from spinel structure after the initiating of reaction by non‐spinel CuO entities. Incorporation of Ni in the spinel structure reveals two positive effects: slowing down the Cu releasing rate and producing even smaller Cu nanoparticles as compared to that of Cu−Al spinel. Since Ni2+ ions in spinel framework cannot be reduced during the catalytic process, we suggest that the remaining defective CuaNib□cAldO4 spinel structure plays a crucial role in stabilizing the formed Cu nanoparticles. The synthesized sample with 0.05 mol Ni per mol Cu shows the best catalytic performance as demonstrated by pretty stable activity during the long‐term catalytic testing up to 2000 h. The findings show great commercial application potentials for the production of H2 from MSR. Just keep on, keepin′ on: Small amounts of Ni modified Cu−Al spinel solid solution catalyst presents enhanced catalytic performance in methanol steam reforming. The defect spinel containing a few Ni2+ and Cu2+ ions can well stabilize Cu nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: Serum circulating microRNAs (c‐miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one‐step branched rolling circle amplification (BRCA) method to measure serum c‐miRNAs levels for early diagnosis of breast cancer. Four c‐miRNAs, c‐miRNA16 (c‐miR‐16), c‐miRNA21 (c‐miR‐21), c‐miRNA155 (c‐miR‐155), and c‐miRNA195 (c‐miR‐195) were isolated from the serum of 49 breast cancer patients (stages I‐IV) and 19 healthy controls, and analyzed using one‐step BRCA. The serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER‐2 over‐expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c‐miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real‐time PCR (qRT‐PCR) method show that the serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes. [ABSTRACT FROM AUTHOR]

Abstract: Potassium‐ion batteries (PIBs) are promising energy storage systems because of the abundance and low cost of potassium. The formidable challenge is to develop suitable electrode materials and electrolytes for accommodating the relatively large size and high activity of potassium. Herein, Bi‐based materials are reported as novel anodes for PIBs. Nanostructural design and proper selection of the electrolyte salt have been used to achieve excellent cycling performance. It is found that the potassiation of Bi undergoes a solid‐solution reaction, followed by two typical two‐phase reactions, corresponding to Bi ↔ Bi(K) and Bi(K) ↔ K5Bi4 ↔ K3Bi, respectively. By choosing potassium bis(fluorosulfonyl)imide (KFSI) to replace potassium hexafluorophosphate (KPF6) in carbonate electrolyte, a more stable solid electrolyte interphase layer is achieved and results in notably enhanced electrochemical performance. More importantly, the KFSI salt is very versatile and can significantly promote the electrochemical performance of other alloy‐based anode materials, such as Sn and Sb. [ABSTRACT FROM AUTHOR]

Iron sulfides have been attracting great attention as anode materials for high-performance rechargeable sodium-ion batteries due to their high theoretical capacity and low cost. In practice, however, they deliver unsatisfactory performance because of their intrinsically low conductivity and volume expansion during charge-discharge processes. Here, a facile in situ synthesis of a 3D interconnected FeS@Fe3C@graphitic carbon (FeS@Fe3C@GC) composite via chemical vapor deposition (CVD) followed by a sulfuration strategy is developed. The construction of the double-layered Fe3C/GC shell and the integral 3D GC network benefits from the catalytic effect of iron (or iron oxides) during the CVD process. The unique nanostructure offers fast electron/Na ion transport pathways and exhibits outstanding structural stability, ensuring fast kinetics and long cycle life of the FeS@Fe3C@GC electrodes for sodium storage. A similar process can be applied for the fabrication of various metal oxide/carbon and metal sulfide/carbon electrode materials for high-performance lithium/sodium-ion batteries. [ABSTRACT FROM AUTHOR]

Melatonin exerts many physiological effects via melatonin receptors, among which the melatonin-2 receptor ( MT2) plays a critical role in circadian rhythm disorders, Alzheimer's disease and other neurological disorders. A melatonin replacement strategy has been tested previously, and MT2 was a critical target during the process. cAMP response element binding ( CREB) is an essential transcription factor for memory formation and could be involved in MT2 signalling. Therefore, the present study was designed to investigate the effects of prophylactic melatonin on inhaled anaesthetic isoflurane-induced cognitive impairment, and to determine whether the protective effects of melatonin are dependent on MT2 and downstream CREB signalling in the hippocampus of aged rats. The results showed that prophylactic melatonin attenuated isoflurane-induced decreases in plasma/hippocampal melatonin levels and cognitive impairment in aged rats. Furthermore, 4P- PDOT, a selective MT2 antagonist, blocked the protective effects of melatonin on isoflurane-induced decreases in both hippocampal MT2 expression and downstream CREB phosphorylation. And 4P- PDOT blocked the attenuation of melatonin on isoflurane-induced memory impairment. Collectively, the results suggest that the protective effects of prophylactic melatonin are dependent on hippocampal MT2- CREB signalling, which could be a potential therapeutic target for anaesthetic-induced cognitive impairment. [ABSTRACT FROM AUTHOR]

This study proposes a model predictive control (MPC)‐based home energy management system for residential microgrid (RM) in which all related information such as the time‐varying information of the load demand, electricity price and renewable energy generations, are all taken into account. A novel finite‐horizon mixed‐integer linear programming problem is iteratively formulated to investigate the optimal control actions of the RM under an MPC framework. Three case studies are conducted to discuss the technical and economic impacts of the responsive electrical and thermal loads, plug‐in hybrid electric vehicles, and electrical and thermal energy storage units. Moreover, a sensitivity analysis is performed to demonstrate the superiority of the proposed approach when forecasts of related information are imperfect. [ABSTRACT FROM AUTHOR]

A novel electrical current applied technique known as flash sintering has been applied to rapidly (within 10 min) densify electrolytes including Ce0.8Gd0.2O1.9 ( GDC20), Ce0.9Gd0.1O1.95 ( GDC10), and Ce0.8Sm0.2O1.9 ( SDC20) for application in Solid Oxide Fuel Cells ( SOFCs). The densification temperature for the three electrolytes was 554°C, 635°C, and 667°C, respectively, which is far below conventional sintering temperatures. All specimens after flash sintering maintained the pure fluorite structure and exhibited a well-densified microstructure. To investigate the flash-sintering mechanism, we have applied Joule heating effect with blackbody radiation theory, and found that this theory could reasonably interpret the flash-sintering phenomenon by matching theoretically calculated temperature with the real temperature. More importantly, one of the materials inherent properties, the electronic conductivity, has been found correlated with the onset of flash sintering, which indicates that the electrons and holes are the primary current carriers during the start of flash-sintering process. As a result, potential densification mechanisms have been discussed in terms of spark plasma discharge. [ABSTRACT FROM AUTHOR]

Cu-Al spinel oxide, which contains a small portion of the CuO phase, has been successfully used in methanol steam reforming (MSR) without prereduction. The omission of prereduction not only avoids the copper sintering prior to the catalytic reaction, but also slows down the copper-sintering rate in MSR. During this process, the CuO phase can initiate MSR at a lower temperature, and CuAl2O4 releases active copper gradually. The catalyst CA2.5-900, calcined at 900 °C with n(Al)/ n(Cu)=2.5, has a higher CuAl2O4 content, higher BET surface area, and smaller CuAl2O4 crystal size. Its activity first increases and then decreases during MSR. Furthermore, both fresh and regenerated CA2.5-900 showed better catalytic performance than the commercial Cu-Zn-Al catalyst. [ABSTRACT FROM AUTHOR]

Melatonin is an endogenous hormone with neuroprotective effects. Melatonin levels in elderly patients are reduced after surgeries that require anaesthesia. Whether reduced melatonin levels are important for postoperative cognitive dysfunction ( POCD) remains unclear. Here, we investigated the effects of melatonin on cognitive dysfunctions induced by isoflurane and mechanisms underlying these effects. Seventy-two 20-month-old Sprague-Dawley rats were randomly divided into six groups (n = 12). These groups included M1 and M10 groups that received intraperitoneal melatonin at 1 mg/kg or 10 mg/kg, respectively, and an ISO group that received 4 hr of inhaled 2% isoflurane. They also included M1+ ISO and M10+ ISO groups that received 1 mg/kg or 10 mg/kg of melatonin plus 4 hr of inhaled 2% isoflurane, respectively, and a control group that received an equal volume of saline. Injections were administered daily for 14 consecutive days. Memory was assessed in the Morris water maze. Plasma and hippocampi were harvested to determine melatonin concentrations and MT1/ MT2 receptor expression. Rats treated only with isoflurane showed significantly longer latencies in Morris water maze test trials compared with the control group, with shorter time in the probe trial ( p < 0.05). Although plasma melatonin levels and MT2 expression in the hippocampus were significantly decreased, MT1 expression was higher in the isoflurane group than in the control group ( p < 0.001). However, these parameters did not significantly vary in animals administered melatonin compared with controls. Isoflurane may induce cognitive dysfunction by influencing melatonin and MT1/ MT2 levels. Melatonin can improve cognitive dysfunction by normalizing plasma melatonin and its receptor levels. [ABSTRACT FROM AUTHOR]

This study explores the ecological and economic impacts of interactions between escaped farmed and wild Atlantic salmon ( Salmo salar, Salmonidae) over generations. An age- and stage-structured bioeconomic model is developed. The biological part of the model includes age-specific life-history traits such as survival rates, fecundity and spawning successes for wild and escaped farmed salmon, as well as their hybrids, while the economic part takes account of use and non-use values of fish stock. The model is simulated under three scenarios using data from the Atlantic salmon fishery and salmon farming in Norway. The social welfare is derived from harvest and wild salmon while the economic benefits of fishing comprise both sea and river fisheries. The results reveal that the wild salmon stock is gradually replaced by salmon with farmed origin, while the total social welfare and economic benefit decline, although not at the same rate as the wild salmon stock. [ABSTRACT FROM AUTHOR]

Potassium‐ion batteries (PIBs) are an emerging, affordable, and environmentally friendly alternative to lithium‐ion batteries, with their further development driven by the need for suitably performing electrode materials capable of reversibly accommodating the relatively large K+. Layer‐structured manganese oxides are attractive as electrodes for PIBs, but suffer from structural instability and sluggish kinetics of K+ insertion/extraction, leading to poor rate capability. Herein, cobalt is successfully introduced at the manganese site in the KxMnO2 layered oxide electrode material and it is shown that with only 5% Co, the reversible capacity increases by 30% at 22 mA g‐1 and by 92% at 440 mA g‐1. In operando synchrotron X‐ray diffraction reveals that Co suppresses Jahn–Teller distortion, leading to more isotropic migration pathways for K+ in the interlayer, thus enhancing the ionic diffusion and consequently, rate capability. The detailed analysis reveals that additional phase transitions and larger volume change occur in the Co‐doped material as a result of layer gliding, with these associated with faster capacity decay, despite the overall capacity remaining higher than the pristine material, even after 500 cycles. These results assert the importance of understanding the detailed structural evolution that underpins performance that will inform the strategic design of electrode materials for high‐performance PIBs. [ABSTRACT FROM AUTHOR]