Enabling High-Performance Layered Li-Rich Oxide Cathodes by Regulating the Formation of Integrated Cation-Disordered Domains.

Layered Li-rich oxide cathode materials are capable of offering high energy density due to their cumulative cationic and anionic redox mechanism during (de)lithiation process. However, the structural instability of the layered Li-rich oxide cathode materials, especially in the deeply delitiated state, results in severe capacity and voltage degradation. Considering the minimal isotropic structural evolution of disordered rock salt oxide cathode during cycling, cation-disordered nano-domains have been controllably introduced into layered Li-rich oxides by co-doping of d0-TM and alkali ions. Combining electrochemical and synchrotron-based advanced characterizations, the incorporation of the phase-compatible cation-disordered domains can not only hinder the oxygen framework collapse along the c axis of layered Li-rich cathode under high operation voltage but also promote the Mn and anionic activities as well as Li+ (de)intercalation kinetics, leading to remarkable improvement in rate capability and mitigation of capacity and voltage decay. With this unique layered/rocksalt intergrown structure, the intergrown cathode yields an ultrahigh capacity of 288.4 mAh g-1 at 0.1 C, and outstanding capacity retention of ≈90.0% with obviously suppressed voltage decay after 100 cycles at 0.5, 1, and 2 C rate. This work provides a new direction toward advanced cathode materials for next-generation Li-ion batteries.

Single-Molecule Assessment of DNA Hybridization Kinetics on Dye-Loaded DNA Nanostructures.

DNA nanostructures offer a versatile platform for precise dye assembly, making them promising templates for creating photonic complexes with applications in photonics and bioimaging. However, despite these advancements, the effect of dye loading on the hybridization kinetics of single-stranded DNA protruding from DNA nanostructures remains unexplored. In this study, the DNA points accumulation for imaging in the nanoscale topography (DNA-PAINT) technique is employed to investigate the accessibility of functional binding sites on DNA-templated excitonic wires. The results indicate that positively charged dyes on DNA frameworks can accelerate the hybridization kinetics of protruded ssDNA through long-range electrostatic interactions. Furthermore, the impacts of various charged dyes and binding sites are explored on diverse DNA frameworks with varying cross-sizes. The research underscores the crucial role of electrostatic interactions in DNA hybridization kinetics within DNA-dye complexes, offering valuable insights for the functionalization and assembly of biomimetic photonic systems.

Mapping Endocytic Vesicular Acidification with a pH-Responsive DNA Nanomachine.

Mapping the endocytic vesicular acidification process is of prior importance to better understand the health and pathological processes of cells. Herein, by integrating a pH-sensitive i-motif and a pair of fluorescence resonance energy transfer (FRET) into a tetrahedral DNA framework (TDF), we develop a pH-responsive DNA nanomachine, allowing for efficient sensing of pH from 7.0 to 5.5 via the pH-triggered spatial proximity modulation of FRET. The inheriting endo-lysosome-targeting ability of TDF enables spatiotemporal tracking of endocytic vesicle acidification during the endosomal maturation process. Analysis of pH-dependent FRET response at single fluorescent spot level reveals the significant difference of endocytic vesicular acidification between normal and cancer cells. The performance of pH-responsive DNA nanomachine underlines its potential for studies on vesicle acidification-related pathologies as a universal platform.

MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence.

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.

Global burden of stroke in adolescents and young adults (aged 15-39 years) from 1990 to 2019: a comprehensive trend analysis based on the global burden of disease study 2019.

INTRODUCTION: The incidence of stroke is rising among individuals aged 15-39. Insufficient research targeting this age group hampers the development of effective strategies. This study analyzes data from the Global Burden of Disease Study 2019 (GBD 2019) to examine trends from 1990 to 2019 and propose future interventions. METHODS: Data on ischemic strokes, intracerebral hemorrhage, and subarachnoid hemorrhage from 1990 to 2019 was collected from the Global Health Data Exchange (GHDx) platform. We used the Annual Average Percentage Change (AAPC) to assess global trends in incidence, prevalence, Disability-Adjusted Life Years (DALYs), and mortality rates across various stroke categories. Joinpoint models identified significant years of trend inflection. Trend analyses were segmented by age, gender, and Sociodemographic Index (SDI). FINDINGS: From 1990 to 2019, the global incidence of ischemic stroke within the adolescents and young adults (AYAs) cohort declined from 1990 to 1999, further decreased from 2000 to 2009, and then increased from 2010 to 2019. The overall AAPC p-value showed no significant difference. Mortality rates for ischemic strokes were consistently reduced during this period. The overall incidence rate of intracerebral hemorrhage has exhibited a downward trend. Meanwhile, the incidence rate of subarachnoid hemorrhage decreased from 1990 to 2009, yet saw a resurgence from 2010 to 2019. Male ischemic stroke incidence grew more than female incidence, but both absolute incidence and rates were higher for females. Differences in SDI levels were observed, with the fastest increase in incidence occurring in low-middle SDI regions, followed by high SDI regions, and the smallest increase in low SDI regions. Conversely, the most rapid decline was noted in high-middle SDI regions, with no significant change observed in middle SDI regions. CONCLUSION: A concerning trend of increasing ischemic stroke incidence, DALYs, and prevalence rates has emerged in the global 15-39 age group, especially among those aged 30-39. This increase is evident across regions with varying SDI classifications. To combat this alarming trend among adolescents and young adults, enhancing preventive efforts, promoting healthier lifestyles, strengthening the healthcare system's responsiveness, and maintaining vigilant epidemiological monitoring is essential.

The structurally conserved TELR region on shelterin protein TPP1 is essential for telomerase processivity but not recruitment.

The shelterin protein TPP1 is involved in both recruiting telomerase and stimulating telomerase processivity in human cells. Assessing the in vivo significance of the latter role of TPP1 has been difficult, because TPP1 mutations that perturb telomerase function tend to abolish both telomerase recruitment and processivity. The Saccharomyces cerevisiae telomerase-associated Est3 protein adopts a protein fold similar to the N-terminal region of TPP1. Interestingly, a previous structure-guided mutagenesis study of Est3 revealed a TELR surface region that regulates telomerase function via an unknown mechanism without affecting the interaction between Est3 and telomerase [T. Rao et al., Proc. Natl. Acad. Sci. U.S.A. 111, 214-218 (2014)]. Here, we show that mutations within the structurally conserved TELR region on human TPP1 impaired telomerase processivity while leaving telomerase recruitment unperturbed, hence uncoupling the two roles of TPP1 in regulating telomerase. Telomeres in cell lines containing homozygous TELR mutations progressively shortened to a critical length that caused cellular senescence, despite the presence of abundant telomerase in these cells. Our findings not only demonstrate that telomerase processivity can be regulated by TPP1 in a process separable from its role in recruiting telomerase, but also establish that the in vivo stimulation of telomerase processivity by TPP1 is critical for telomere length homeostasis and long-term viability of human cells.

Efficacy of Neuroendoscopy Surgery Combined With Postoperative Lokomat Rehabilitation Training in Patients With Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: To explore the effects of neuroendoscopy surgery combined with postoperative Lokomat rehabilitation training on patients with hypertensive cerebral hemorrhage. METHODS: A total of 88 patients with hypertensive cerebral hemorrhage who underwent surgical treatment in our hospital were retrospectively analyzed. They were divided into a study group and a conventional group with 44 patients in each group. The patients in the 2 groups were compared regarding operation-related conditions, hospital stay, preoperative and postoperative functional status scores, and postoperative complications. RESULTS: The operation time, intraoperative blood loss, hospital stays, and hematoma clearance rate of the study group were significantly better than those of the conventional group (P<0.001). Regarding scores of related functional status, there was no significant difference between the 2 groups before operation (P>0.05). The different scores of the study group were significantly better than those of the conventional group 1 month after the operation (P<0.05). Regarding complications, the study group also has significant advantages, with only one case of rebleeding. CONCLUSION: Compared to the traditional approach of small bone window craniotomy followed by postoperative Lokomat rehabilitation training, the combination of neuroendoscopy surgery and Lokomat training proves to be more efficient. This approach can effectively reduce the operating time and hospital stay of patients with hypertensive intracerebral hemorrhage, minimize intraoperative blood loss, improve the hematoma clearance rate, and lower the incidence of postoperative complications.

YEATS2 regulates the activation of TAK1/NF-κB pathway and is critical for pancreatic ductal adenocarcinoma cell survival.

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is poor despite diagnostic progress and new chemotherapeutic regimens. Constitutive activation of NF-κB is frequently observed in PDAC. In this study, we found that YEATS2, a scaffolding protein of ATAC complex, was highly expressed in human PDAC. Depletion of YEATS2 reduced the growth, survival, and tumorigenesis of PDAC cells. The binding of YEATS2 is crucial for maintaining TAK1 activation and NF-κB transcriptional activity. Of importance, our results reveal that YEATS2 promotes NF-κB transcriptional activity through modulating TAK1 abundance and directly interacting with NF-κB as a co-transcriptional factor.

Analysis of Effect of Minimally Invasive Fourth-ventricle Hematoma Removal for Patients with Intraventricular Hemorrhage Casting and Influence of Feedback Early Rehabilitation on Postoperative Neurological Function.

Purpose: To investigate the therapy effect of minimally invasive fourth-ventricle hematoma removal (MIFHR) for patients with intraventricular hemorrhage (IVH) casting and the influence of feedback early rehabilitation on post-operative neurological function. Methods: Eighty patients with IVH casting were enrolled from January 2019 to December 2020 in this retrospective study. Forty patients receiving MIFHR with feedback early rehabilitation were divided into the observational group, while the others receiving bilateral external ventricular drainage with traditional rehabilitation were divided into the control group. Glasgow Coma Scale (GCS) and neurological function before and after operation were compared between the two groups. In addition, hematoma clearance rate three days after surgery, drainage duration, hospitalization time, motor function and activity daily living (ADL) six months after surgery, and incidence of complications were also compared. Results: No significant differences were observed in GCS score and neurological function before surgery between the two groups (both P > .05). At the same time, there were significant differences GCS score and neurological function after surgery (both P < .05). Hematoma clearance rate three days after surgery, drainage duration, hospitalization time, and incidence of complications in the observational group were lower than those in the control group (all P < .05). In contrast, motor function and ADL six months after surgery were better in the observational group (both P < .05). Conclusion: MIFHR combined with feedback early rehabilitation is conducive to the recovery of neurological function, motor function, and ADL without increasing the incidence of complications.

Self-adaption and texture generation: A hybrid loss function for low-dose CT denoising.

BACKGROUND: Deep learning has been successfully applied to low-dose CT (LDCT) denoising. But the training of the model is very dependent on an appropriate loss function. Existing denoising models often use per-pixel loss, including mean abs error (MAE) and mean square error (MSE). This ignores the difference in denoising difficulty between different regions of the CT images and leads to the loss of large texture information in the generated image. PURPOSE: In this paper, we propose a new hybrid loss function that adapts to the noise in different regions of CT images to balance the denoising difficulty and preserve texture details, thus acquiring CT images with high-quality diagnostic value using LDCT images, providing strong support for condition diagnosis. METHODS: We propose a hybrid loss function consisting of weighted patch loss (WPLoss) and high-frequency information loss (HFLoss). To enhance the model's denoising ability of the local areas which are difficult to denoise, we improve the MAE to obtain WPLoss. After the generated image and the target image are divided into several patches, the loss weight of each patch is adaptively and dynamically adjusted according to its loss ratio. In addition, considering that texture details are contained in the high-frequency information of the image, we use HFLoss to calculate the difference between CT images in the high-frequency information part. RESULTS: Our hybrid loss function improves the denoising performance of several models in the experiment, and obtains a higher peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). Moreover, through visual inspection of the generated results of the comparison experiment, the proposed hybrid function can effectively suppress noise and retain image details. CONCLUSIONS: We propose a hybrid loss function for LDCT image denoising, which has good interpretation properties and can improve the denoising performance of existing models. And the validation results of multiple models using different datasets show that it has good generalization ability. By using this loss function, high-quality CT images with low radiation are achieved, which can avoid the hazards caused by radiation and ensure the disease diagnosis for patients.

Towards an Optimized Distributed Message Queue System for AIoT Edge Computing: A Reinforcement Learning Approach.

The convergence of artificial intelligence and the Internet of Things (IoT) has made remarkable strides in the realm of industry. In the context of AIoT edge computing, where IoT devices collect data from diverse sources and send them for real-time processing at edge servers, existing message queue systems face challenges in adapting to changing system conditions, such as fluctuations in the number of devices, message size, and frequency. This necessitates the development of an approach that can effectively decouple message processing and handle workload variations in the AIoT computing environment. This study presents a distributed message system for AIoT edge computing, specifically designed to address the challenges associated with message ordering in such environments. The system incorporates a novel partition selection algorithm (PSA) to ensure message order, balance the load among broker clusters, and enhance the availability of subscribable messages from AIoT edge devices. Furthermore, this study proposes the distributed message system configuration optimization algorithm (DMSCO), based on DDPG, to optimize the performance of the distributed message system. Experimental evaluations demonstrate that, compared to the genetic algorithm and random searching, the DMSCO algorithm can provide a significant improvement in system throughput to meet the specific demands of high-concurrency AIoT edge computing applications.

Expansion of targetable sites for the ribonucleoprotein-based CRISPR/Cas9 system in the silkworm Bombyx mori.

BACKGROUND: With the emergence of CRISPR/Cas9 technology, multiple gene editing procedures became available for the silkworm. Although binary transgene-based methods have been widely used to generate mutants, delivery of the CRISPR/Cas9 system via DNA-free ribonucleoproteins offers several advantages. However, the T7 promoter that is widely used in the ribonucleoprotein-based method for production of sgRNAs in vitro requires a 5' GG motif for efficient initiation. The resulting transcripts bear a 5' GG motif, which significantly constrains the number of targetable sites in the silkworm genome. RESULTS: In this study, we used the T7 promoter to add two supernumerary G residues to the 5' end of conventional (perfectly matched) 20-nucleotide sgRNA targeting sequences. We then asked if sgRNAs with this structure can generate mutations even if the genomic target does not contain corresponding GG residues. As expected, 5' GG mismatches depress the mutagenic activity of sgRNAs, and a single 5' G mismatch has a relatively minor effect. However, tests involving six sgRNAs targeting two genes show that the mismatches do not eliminate mutagenesis in vivo, and the efficiencies remain at useable levels. One sgRNA with a 5' GG mismatch at its target performed mutagenesis more efficiently than a conventional sgRNA with 5' matched GG residues at a second target within the same gene. Mutations generated by sgRNAs with 5' GG mismatches are also heritable. We successfully obtained null mutants with detectable phenotypes from sib-mated mosaics after one generation. CONCLUSIONS: In summary, our method improves the utility and flexibility of the ribonucleoprotein-based CRISPR/Cas9 system in silkworm.

Relationship between electrode position of deep brain stimulation and motor symptoms of Parkinson's disease.

BACKGROUND: To investigate the relationship between the position of bilateral STN-DBS location of active contacts and the clinical efficacy of STN-DBS on motor symptoms in Parkinson's disease (PD) patients. METHODS: Retrospectively analyze the clinical data of 57 patients with PD who underwent bilateral STN-DBS from March 2018 to December 2018. Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39) before operation and within 6 months after operation, determine the location of activated contacts and volume of tissue activated (VTA) in the Montreal Neurological Institute (MNI) space, and analyze their correlation with the improvement rate of motor symptoms (UPDRS-III score improvement rate). RESULTS: After 6 months of follow up, the UPDRS-III scores of 57 patients (Med-off) were improved by 55.4 ± 18.9% (P<0.001) compared with that before operation. The improvement rate of PDQ-39 scores [(47.4 ± 23.2)%, (P < 0.001)] and the reduction rate of LEDD [(40.1 ± 24.3)%, (P < 0.01)] at 6 months postoperation were positively correlated with the improvement rate of motor symptoms (Med-off)(PDQ-39:r = 0.461, P<0.001; LEDD: r = 0.354, P = 0.007), the improvement rate of UPDRS-III (Med-off) and the Z-axis coordinate of the active contact in the MNI space were positively correlated (left side: r = 0.349,P = 0.008;right side: r = 0.369,P = 0.005). In the MNI space, there was no correlation between the UPDRS-III scores improvement rate (Med-off) at 6 months after operation and bilateral VTA in the STN motor subregion, STN associative subregion and STN limbic subregion of the active electrode contacts of 57 patients (all P > 0.05). At 6 months after surgery, the difference between the Z-axis coordinate in the different improvement rate subgroups(<25, 25 to 50%, and>50%) in the MNI space was statistically significant (left side: P = 0.030; right side: P = 0.024). In the MNI space, there was no statistically significant difference between the groups in the VTA of the electrode active contacts (all P > 0.05). CONCLUSION: STN-DBS can improve the motor symptoms of PD patients and improve the quality of life. The closer the stimulation is to the STN dorsolateral sensorimotor area, the higher the DBS is to improve the motor symptoms of PD patients.

Modified Model for Diagnosing Breast Imaging Reporting and Data System Category 3 to 5 Breast Lesions: Retrospective Analysis and Nomogram Development.

OBJECTIVES: The aim of this study was to explore a modified model to simplify the diagnostic process for American College of Radiology Breast Imaging Reporting and Data System category 3 to 5 breast lesions and evaluate the model's diagnostic efficacy. METHODS: A retrospective review was conducted of breast lesions examined by B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) and diagnosed by histopathologic examination from October 2016 to August 2019. The US characteristics of a combined model (US + CEUS model) with relatively high diagnostic value were selected by a lasso regression analysis to establish a modified model. Two nomograms were developed. The results were internally validated by bootstrap resampling. RESULTS: Overall, 206 breast lesions in 198 patients, 136 benign and 70 malignant, were included. Ultrasound characteristics included in the modified model were shape, margin, microcalcification, enhanced intensity, enhanced scope, and enhanced time. For the US + CEUS model and modified model, sensitivities were 94.3% and 93.3%; specificities were 85.9% and 81.4%; accuracies were 89.3% and 88.7% and areas under the curve were 0.957 and 0.944, respectively. No statistically significant differences were seen in the diagnostic efficacies of the models (P = .097). Bootstrap-corrected sensitivities, specificities. and accuracies of the models were consistent with these results. Bootstrap-corrected areas under the curve for the US + CEUS model and the modified model were 0.955 and 0.940, respectively. CONCLUSIONS: The modified model with fewer indicators conveniently and effectively diagnosed the malignancy of Breast Imaging Reporting and Data System category 3 to 5 breast lesions without reducing diagnostic efficacy.

Antifungal activity of water-soluble products obtained following the liquefaction of cornstalk with sub-critical water.

Cornstalks are the leftover leaves and stems in a field after corn harvest. They are a potential biomass resource but are underutilized in agricultural production systems. To examine the chemical components in cornstalks and their corresponding functions, blocky cornstalks were treated in water at temperatures of 190, 210, 230, 250, and 270 °C in a high-pressure reactor. Water-soluble products (WSPs) were extracted from these treatments, and their chemical compositions were analyzed using gas chromatography-mass spectrometry (GC-MS), and their antifungal activities were determined using a bioassay. It was found that WSPs contained 28.7-40.1% phenols, 27.9-36.6% ketones, 0-2.6% alcohols, 4.9-10.1% esters, 5.4-7.8% organic acids, 1.3-12% aldehydes, and 5.5-18.4% of other organic compounds such as nitrogen- and sulfur-containing compounds, furan compounds, and benzene compounds. The inhibition the growth of the plant pathogen Fusarium oxysporum by WSPs was affected by temperature. WSP-270 (obtained at 270 °C) exhibited the best growth-inhibition efficacy. Under a biomicroscope, WSP-270-treated F. oxysporum showed a deformed and swollen hypha, and an increased number of bifurcations, as well as an expansion of growing apexes of new bifurcations. Therefore, the antifungal activity of WSPs could be used to manage soilborne plant pathogens.

An N-terminal Flag-tag impairs TPP1 regulation of telomerase function.

The shelterin protein complex protects natural chromosome ends from being recognized as DNA damage sites and also regulates the synthesis of telomeric repeats by telomerase. TPP1, a shelterin subunit that is essential for telomerase extension of telomeres, has been studied intensively in recent years. Many such studies utilize epitope tagged TPP1, but it is unclear how the tags may affect the multiple cellular functions of TPP1. Here we analyzed the effect of adding a 3x Flag epitope tag to the N- or C-terminus of TPP1. While the position of the tag did not affect TPP1's interaction within the shelterin complex or its localization to telomeres, the N-terminal Flag tag on TPP1 impaired telomerase function, resulting in reduced telomerase processivity in vitro and a failure to stimulate telomere elongation in vivo. The C-terminally Flag-tagged TPP1, in contrast, behaved similarly to untagged TPP1 in all functional aspects examined. These findings suggest that caution is required when utilizing epitope tagged TPP1 to study its regulation of telomerase function.

Spatial Confined Synergistic Enzymes with Enhanced Uricolytic Performance and Reduced Toxicity for Effective Gout Treatment.

Confinement of urate oxidase with detoxifying enzymes into multienzyme architecture is an appealing approach for gout treatment due to its capability to decompose serum uric acid without generation of H2 O2 . However, most of these strategies involve chemical modifications to the enzymes and barely consider enhancing the stability of the multienzyme architectures particularly against proteolysis, which significantly dampened its catalytic activity and in vivo stability. Herein, a novel strategy to prepare multienzyme nanoclusters with highly uricolytic activity and enhanced stability is demonstrated. With the close proximation, catalase can effectively decompose the H2 O2 generated by uricase during uricolysis. Moreover, with a shell structure constructed with polyethylene glycol, the nanocluster achieves great performance in reducing the nonspecific serum protein adsorptions and proteases digestion, leading to an enhanced circulation time after the intravenous administration. Such complementary multienzyme nanoclusters realize the long-term therapeutic effect in the management of serum uric acid level, without any toxicity or undesired immune responses in vivo. This work mimics the synergistic effect of protein complex in nature and can be further developed to a general method for the construction of multienzyme nanoclusters, which provides new opportunities for utilizing therapeutic enzymes for the treatment of metabolic diseases.

The terminal telomeric DNA sequence determines the mechanism of dysfunctional telomere fusion.

Mammalian telomeres consist of tandem DNA repeats that bind protective protein factors collectively termed shelterins. Telomere disruption typically results in genome instability induced by telomere fusions. The mechanism of telomere fusion varies depending on the means of telomere disruption. Here, we investigate telomere fusions caused by overexpression of mutant telomerases that add mutated telomeric repeats, thereby compromising shelterin binding to telomeric termini. While all mutant telomeric sequences tested induced heterodicentric chromosome fusions in ATM-competent cells, only those mutant repeat sequences with significant self complementarity induced ATM-independent sister chromatid and isodicentric chromosome fusions. Thus, once a telomere becomes dysfunctional, the terminal telomeric sequence itself determines the fate of that telomere. These results suggest that annealing of self-complementary DNA sequence engages an alternative telomere fusion pathway in human cells, and provide one explanation for the conspicuous lack of self complementarity in the majority of known naturally occurring eukaryotic telomeric sequences.

The Shelterin TIN2 Subunit Mediates Recruitment of Telomerase to Telomeres.

Dyskeratosis Congenita (DC) is a heritable multi-system disorder caused by abnormally short telomeres. Clinically diagnosed by the mucocutaneous symptoms, DC patients are at high risk for bone marrow failure, pulmonary fibrosis, and multiple types of cancers. We have recapitulated the most common DC-causing mutation in the shelterin component TIN2 by introducing a TIN2-R282H mutation into cultured telomerase-positive human cells via a knock-in approach. The resulting heterozygous TIN2-R282H mutation does not perturb occupancy of other shelterin components on telomeres, result in activation of telomeric DNA damage signaling or exhibit other characteristics indicative of a telomere deprotection defect. Using a novel assay that monitors the frequency and extension rate of telomerase activity at individual telomeres, we show instead that telomerase elongates telomeres at a reduced frequency in TIN2-R282H heterozygous cells; this recruitment defect is further corroborated by examining the effect of this mutation on telomerase-telomere co-localization. These observations suggest a direct role for TIN2 in mediating telomere length through telomerase, separable from its role in telomere protection.

Designing 3D interconnected continuous nanoporous Co/CoO core-shell nanostructure electrodes for a high-performance pseudocapacitor.

A high-performance supercapacitor electrode is designed and fabricated with the 3D interconnected continuous nanoporous Co/CoO core-shell hybrid nanostructure grown on nickel foam. The Co/CoO core-shell hybrid nanostructures are obtained via a hydrothermal method, followed by high-temperature annealing in hydrogen atmosphere, and finally placed in air at 50 °C for 1 h. The Co/CoO core-shell nanostructure assembled by a conductive metal-core and a CoO shell, brings low resistance, high specific capacitance of 5.632 F cm-2 and good capability stability (81.5% capacitance retention after 6000 cycles). An asymmetric supercapacitor device built by the Co/CoO (positive electrode) and activated carbon (negative electrode) can deliver a working voltage of 1.7 V and display a high energy density of 0.002 67 Wh cm-2 at a power density of 0.001 62 W cm-2, which is far superior to that of a supercapacitor at a similar power density.