The structure of the archaeal nuclease RecJ2 implicates its catalytic mechanism and inability to interact with GINS.

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to ssDNA; however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.

Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.

Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.

The biochemical characterization of a TatD nuclease from Thermus thermophilus.

Nucleases play pivotal roles in DNA repair and apoptosis. Moreover, they have various applications in biotechnology and industry. Among nucleases, TatD has been characterized as an exonuclease with various biological functions in different organisms. Here, we biochemically characterized the potential TatD nuclease from Thermus thermophilus. The tatD gene from T. thermophilus was cloned, then the recombinant TatD nuclease was expressed and purified. Our results revealed that the TthTatD nuclease could degrade both single-stranded and double-stranded DNA, and its activity is dependent on the divalent metal ions Mg2+ and Mn2+. Remarkably, the activity of TthTatD nuclease is highest at 37 °C and decreases with increasing temperature. TthTatD is not a thermostable enzyme, even though it is from a thermophilic bacterium. Based on the sequence similarity and molecular docking of the DNA substrate into the modeled TthTatD structure, several key conserved residues were identified and their roles were confirmed by analyzing the enzymatic activities of the site-directed mutants. The residues E86 and H149 play key roles in binding metal ions, residues R124/K126 and K211/R212 had a critical role in binding DNA substrate. Our results confirm the enzymatic properties of TthTatD and provide a primary basis for its possible application in biotechnology.

Aging adipose tissue, insulin resistance, and type 2 diabetes.

With the increase of population aging, the prevalence of type 2 diabetes (T2D) is also rising. Aging affects the tissues and organs of the whole body, which is the result of various physiological and pathological processes. Adipose tissue has a high degree of plasticity and changes with aging. Aging changes the distribution of adipose tissue, affects adipogenesis, browning characteristics, inflammatory status and adipokine secretion, and increases lipotoxicity. These age-dependent changes in adipose tissue are an important cause of insulin resistance and T2D. Understanding adipose tissue changes can help promote healthy aging process. This review summarizes changes in adipose tissue ascribable to aging, with a focus on the role of aging adipose tissue in insulin resistance and T2D.

Optimizing irrigation and nitrogen addition to balance grassland biomass production with greenhouse gas emissions: A mesocosm study.

Achieving a balance between greenhouse gas mitigation and biomass production in grasslands necessitates optimizing irrigation frequency and nitrogen addition, which significantly influence grassland productivity and soil nitrous oxide emissions, and consequently impact the ecosystem carbon dioxide exchange. This study aimed to elucidate these influences using a controlled mesocosm experiment where bermudagrass (Cynodon dactylon L.) was cultivated under varied irrigation frequencies (daily and every 6 days) with (100 kg ha-1) or without nitrogen addition; measurements of net ecosystem carbon dioxide exchange, ecosystem respiration, soil respiration, and nitrous oxide emissions across two cutting events were performed as well. The findings revealed a critical interaction between water-filled pore space, regulated by irrigation, and nitrogen availability, with the latter exerting a more substantial influence on aboveground biomass growth and ecosystem carbon dioxide exchange than water availability. Moreover, the total dry matter was significantly higher with nitrogen addition compared to without nitrogen addition, irrespective of the irrigation frequency. In contrast, soil nitrous oxide emissions were observed to be significantly higher with increased irrigation frequency and nitrogen addition. The effects of nitrogen addition on soil respiration components appeared to depend on water availability, with autotrophic respiration seeing a significant rise with nitrogen addition under limited irrigation (5.4 ± 0.6 µmol m-2 s-1). Interestingly, the lower irrigation frequency did not result in water stress, suggesting resilience in bermudagrass. These findings highlight the importance of considering interactions between irrigation and nitrogen addition to optimize water and nitrogen input in grasslands for a synergistic balance between grassland biomass production and greenhouse gas emission mitigation.

NEAT1 inhibits the angiogenic activity of cerebral arterial endothelial cells by inducing the M1 polarization of microglia through the AMPK signaling pathway.

BACKGROUND: Enhancing angiogenesis may be an effective strategy to promote functional recovery after ischemic stroke. Inflammation regulates angiogenesis. Microglia are crucial cells that initiate inflammatory responses after various brain injuries. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a role in regulating brain injury. This study aimed to explore the effects of NEAT1-regulated microglial polarization on the neovascularization capacity of cerebrovascular endothelial cells and the underlying molecular regulatory mechanisms. METHODS: Mouse cerebral arterial endothelial cells (mCAECs) were co-cultured with BV-2 cells in different groups using a Transwell system. NEAT1 expression levels were measured by fluorescence quantitative reverse transcription PCR. Levels of IL-1ß, IL-6, TNF-α, Arg-1, IL-4, and IL-10 were determined using ELISA. Expression levels of CD86 and CD163 were detected by immunofluorescence. The neovascularization capacity of mCAECs was assessed using CCK-8, Transwell, Transwell-matrigel, and tube formation assays. Label-free quantification proteomics was carried out to identify differentially expressed proteins. Protein levels were measured by Western blotting. RESULTS: NEAT1 overexpression induced M1 polarization in BV-2 cells, whereas NEAT1 knockdown blocked lipopolysaccharide-induced M1 polarization in microglia. NEAT1-overexpressing BV-2 cells suppressed the angiogenic ability of mCAECs, and NEAT1-knocking BV-2 cells promoted the angiogenic ability of mCAECs under lipopolysaccharide treatment. Label-free quantitative proteomic analysis identified 144 upregulated and 131 downregulated proteins that were induced by NEAT1 overexpression. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed proteins. Further verification showed that NEAT1 inactivated the AMPK signaling pathway. Moreover, the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide reversed the effect of NEAT1 on BV-2 polarization and the regulatory effect of NEAT1-overexpressing BV-2 cells on the angiogenic ability of mCAECs. CONCLUSIONS: NEAT1 inhibits the angiogenic activity of mCAECs by inducing M1 polarization of BV-2 cells through the AMPK signaling pathway. This study further clarified the impact and mechanism of NEAT1 on microglia and the angiogenic ability of cerebrovascular endothelial cells.

High Moisture-Barrier Performance of Double-Layer Graphene Enabled by Conformal and Clean Transfer.

Graphene films that can theoretically block almost all molecules have emerged as promising candidate materials for moisture barrier films in the applications of organic photonic devices and gas storage. However, the current barrier performance of graphene films does not reach the ideal value. Here, we reveal that the interlayer distance of the large-area stacked multilayer graphene is the key factor that suppresses water permeation. We show that by minimizing the gap between the two monolayers, the water vapor transmission rate of double-layer graphene can be as low as 5 × 10-3 g/(m2 d) over an A4-sized region. The high barrier performance was achieved by the absence of interfacial contamination and conformal contact between graphene layers during layer-by-layer transfer. Our work reveals the moisture permeation mechanism through graphene layers, and with this approach, we can tailor the interlayer coupling of manually stacked two-dimensional materials for new physics and applications.

Enhanced body shape change coupled with PA is the key to hypertension management for urban residents.

The present study aimed to assess the relationship between body shape, physical activity (PA), and systolic blood pressure (SBP) and diastolic blood pressure (DBP). A novel visualization method was used to examine the effects of body shape combined with physical activity on hypertension. Data from 54,303 participants were obtained from the China Health and Nutrition Survey (CHNS) and analyzed using logistic regression models and standardized regression coefficients of linear models. These models were used to explore factors and effects of body shape indices and other parameters on SBP and DBP. The logistic regression model revealed that compared to transport-related PA, the aggregated variables (weight and waist) were associated with a 2.44-fold and 1.65-fold increase in the risk of hypertension, respectively (p < .05). The average aggregated standardized coefficient of the linear model, based on 1000 bootstrap resamples, indicated that the Base Shape group had the strongest explanatory power for hypertension, followed by the Habits group. However, the explanatory power of the PA group was around 10 and 22 times lower than that of the Base Shape group for DBP and SBP, respectively (p < .05). These results demonstrate that increasing physical activity, with emphasizing a healthy body shape, and adopting positive lifestyle habits can effectively contribute to the prevention and control of hypertension.

Finite element analysis and clinical application of 3D-printed Ti alloy implant for the reconstruction of mandibular defects.

BACKGROUND: The reconstruction of segmental defect of the mandible has always been a challenge. The customized reconstruction plate without a bone graft is also considered a transitional means of rehabilitation and reconstruction in some cases. METHODS: This study evaluated the biomechanical behaviors of customized plates with different structural designs comparing with commercial plates using the finite element method in reconstrution of the lateral mandible defect. RESULTS: Simulations revealed the stress state in the plate bodies, bone tissues and screws were associated with the width, height, thickness of the plates as well as the distribution of screws. In all of the groups, the system of 16 mm-high, 2.8 mm-thick customized reconstruction plate with 10 screws was considered to be the most ideal design because of the most harmonious biomechanical state. What's more, the stress shielding effects were not obvious in this experiment. Based on the above findings, we conducted a clinical case analysis to verify the mechanical properties of customized reconstruction and obtained a satisfactory operation result. CONCLUSIONS: The results show that by adjusting the contour parameters of the reconstruction plates, an ideal and reliable customized plate can be manufactured. And the customized 3D-printed Ti alloy implant will be a new way to achieve mandibular reconstruction in patients unable to perform autologous bone graft surgery. TRIAL REGISTRATION: The present trial has been registered with ChiCTR, the registration number is ChiCTR 2,000,038,973 on 11/10/2020.

MdMPK3 and MdMPK6 fine-tune MdWRKY17-mediated transcriptional activation of the melatonin biosynthesis gene MdASMT7.

Melatonin (N-acetyl-5-methoxytryptamine) is a potent reactive oxygen species (ROS) scavenger that increases the biotic and abiotic stress tolerance in plants. The signaling and regulation pathways of melatonin in plants remain elusive. Here, we report that transgenic apple (Malus domestica) plants overexpressing the transcription factor gene, MdWRKY17, have higher melatonin contents and lower ROS levels than those of control, while the MdWRKY17 RNA interference (RNAi) lines show the reversed phenotype. The binding of MdWRKY17 to N-acetylserotonin O-methyltransferase7 (MdASMT7) directly promotes the MdASMT7 expression in the in vitro and in vivo. MdASMT7 is a melatonin synthase that localizes to the plasma membrane. MdASMT7 overexpression rescued the lower melatonin contents of MdWRKY17-RNAi lines, confirming the role of MdWRKY17-MdASMT7 module in melatonin biosynthesis in apple. Furthermore, melatonin treatment activated the mitogen-activated kinases (MPKs) MdMPK3 and MdMPK6, which phosphorylate MdWRKY17 to promote transcriptional activation of MdASMT7. RNAi-mediated silencing of MdMPK3/6 decreases MdASMT7 expression in transgenic apple plants overexpressing MdWRKY17, which further confirms MdMPK3/6 fine-tunes MdWRKY17-mediated MdASMT7 transcription. This also forms a positive loop that melatonin activates MdMPK3/6 and thus accelerates the biosynthesis of itself via triggering MdMPK3/6-MdWRKY17-MdASMT7 pathway. This novel melatonin regulatory pathway not only have dissected the molecular mechanisms of melatonin biosynthesis but also provided an alternative approach for generating transgenic melatonin-rich apples which may benefits to human health.

Indoloquinazoline alkaloids with cardiomyocyte protective activity against cold ischemic injury from Aspergillus clavatonanicus.

The arthropod-associated fungi have been demonstrated to be a remarkable producer of structurally captivating and bioactive secondary metabolites for drug discovery. In this study, eleven new indoloquinazoline alkaloids, namely aspergilloids A-K (1-11), along with five known congeners (12-16), were obtained from fungus Aspergillus clavatonanicus, which was isolated from the gut of a centipede collected in our Tongji campus. All these compounds were rarely defined by a 6/5/5 indolone ring system in conjugation with a five-membered spiral ring (1-5 and 10-16) or an opening five-membered spiral ring (6-9). Their structures were elucidated by widespread spectroscopic analyses, mainly including HRESIMS and 1D and 2D NMR data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data analyses. The cardiomyocyte protective activity assay revealed that compounds 1, 2, 5, 12-14, and 16 ameliorated cold ischemic injury at 48 h post cold ischemia (CI), and compounds 1, 5, and 14 prevented cold ischemia induced Ser9 dephosphorylation of GSK3ß at 12 h post CI. Our current study highlights indoloquinazoline alkaloids as the first class of natural cardiomyocyte protective agents against cold ischemic injury, which furnishes promising lead molecules for the development of new cardioprotectants in heart transplantation medicine.

A reappraisal of the phylogeny and historical biogeography of Sparganium (Typhaceae) using complete chloroplast genomes.

BACKGROUND: Sparganium (Typhaceae) is a widespread temperate genus of ecologically important aquatic plants. Previous reconstructions of the phylogenetic relationships among Sparganium species are incompletely resolved partly because they were based on molecular markers comprising < 7,000 bp. Here, we sequenced and assembled the complete chloroplast genomes from 19 Sparganium samples representing 15 putative species and three putative subspecies in order to explore chloroplast genome evolution in this genus, clarify taxonomic lineages, estimate the divergence times of Sparganium species, and reconstruct aspects of the biogeographic history of the genus. RESULTS: The 19 chloroplast genomes shared a conserved genome structure, gene content, and gene order. Our phylogenomic analysis presented a well-resolved phylogeny with robust support for most clades. Non-monophyly was revealed in three species: S. erectum, S. eurycarpum, and S. stoloniferum. Divergence time estimates suggest that the two subgenera of Sparganium split from each other ca. 30.67 Ma in the middle Oligocene. The subgenus Xanthosparganium diversified in the late Oligocene and Miocene, while the subgenus Sparganium diversified in the late Pliocene and Pleistocene. Ancestral area reconstruction suggested that the two subgenera may have originated in East Eurasia and North America. CONCLUSION: The non-monophyletic nature of three putative species underscores the necessity of taxonomic revision for Sparganium: S. stoloniferum subsp. choui may be more appropriately identified as S. choui, and subspecies of S. erectum may be in fact distinct species. The estimated diversification times of the two subgenera correspond to their species and nucleotide diversities. The likely ancestral area for most of subgenus Xanthosparganium was East Eurasia and North America from where it dispersed into West Eurasia and Australia. Most of subgenus Sparganium likely originated in North America and then dispersed into Eurasia. Our study demonstrates some of the ways in which complete chloroplast genome sequences can provide new insights into the evolution, phylogeny, and biogeography of the genus Sparganium.

COVID-19 and mental health in Australia - a scoping review.

BACKGROUND: The COVID-19 outbreak has spread to almost every country around the world and caused more than 3 million deaths. The pandemic has triggered enormous disruption in people's daily lives with profound impacts globally. This has also been the case in Australia, despite the country's comparative low mortality and physical morbidity due to the virus. This scoping review aims to provide a broad summary of the research activity focused on mental health during the first 10 months of the pandemic in Australia. RESULTS: A search of the Australian literature was conducted between August-November 2020 to capture published scientific papers, online reports and pre-prints, as well as gaps in research activities. The search identified 228 unique records in total. Twelve general population and 30 subpopulation group studies were included in the review. CONCLUSIONS: Few studies were able to confidently report changes in mental health driven by the COVID-19 context (at the population or sub-group level) due to a lack of pre-COVID comparative data and non-representative sampling. Never-the-less, in aggregate, the findings show an increase in poor mental health over the early period of 2020. Results suggest that young people, those with pre-existing mental health conditions, and the financially disadvantaged, experienced greater declines in mental health. The need for rapid research appears to have left some groups under-researched (e.g. Culturally and Linguistically Diverse populations and Indigenous peoples were not studied), and some research methods under-employed (e.g. there was a lack of qualitative and mixed-methods studies). There is a need for further reviews as the follow-up results of longitudinal studies emerge and understandings of the impact of the pandemic are refined.

The Association of Blood Urea Nitrogen to Creatinine Ratio and the Prognosis of Critically Ill Patients with Cerebral Infarction: A Cohort Study.

Background: To evaluate the association between blood urea nitrogen (BUN) to creatinine (Cr) (BUN/Cr) ratio and the in-hospital mortality of critically ill patients with cerebral infarction in intensive care unit (ICU). Methods: In this cohort study, the data of 3059 participants with cerebral infarction were collected from the Medical Information Mart for Intensive Care (MIMIC)-III and the MIMIC-IV database. After propensity score matching (PSM) on age and gender, 2085 people were involved in and divided into the alive group (n = 1390) and the dead group (n = 695) based on the results of follow-up. Multivariate logistic analyses were applied to identify the confounders and the association between BUN/Cr and mortality of cerebral infarction. Results: The median follow-up time was 10.5 days. Among 2778 participants, 695 were dead at the end of follow-up. Univariate analysis revealed that BUN/Cr [risk ratio (RR) = 1.01, 95% confidence interval (CI): 1.01-1.02] might be associated with the in-hospital mortality of cerebral infarction patients. After adjusting for respiratory failure, malignant cancer, anticoagulation, liver disease, white blood cell (WBC), red cell distribution width (RDW), glucose, bicarbonate, and temperature, BUN/Cr had week correlation with the increased risk of in-hospital mortality of cerebral infarction patients (RR = 1.01, 95% CI: 1.01-1.02). Conclusion: This study evaluated the association between BUN/Cr and the in-hospital mortality of cerebral infarction patients in ICU and found that BUN/Cr had weak correlation with the increased risk of in-hospital mortality of patients with cerebral infarction in ICU especially in males and those with respiratory failure, malignant cancer, and without liver disease, as well as those receiving anticoagulation.

Linguistic barriers and healthcare in China: Chaoshan vs. Mandarin.

BACKGROUND: China has 129 dialects with Mandarin as the standard and Chaoshan as the major dialect of the Chaoshan region in Guangdong. This study aimed to describe the dialect competence and usage, communication difficulty, impact of linguistic barriers, and subjective experience in healthcare. METHODS: Healthcare providers (n = 234) and healthcare consumers (n = 483) at two tertiary teaching hospitals in Shantou, Chaoshan region participated in an anonymous survey. RESULTS: Chaoshan and Mandarin were spoken respectively by ca. 80% and 6.1% of the participants. Monolinguals accounted for 28.5%, including 16.8% of Chaoshan-speaking healthcare providers and 18% of Mandarin-speaking healthcare consumers. The monolinguals preferentially used their competent dialect (Ps < 0.001) and had significant communication difficulties (Ps < 0.0001), with the mean (SD) score of 3.06 (0.96) out of 4 with Mandarin for healthcare providers and 2.18 (1.78) and 1.64 (1.40) with Mandarin and Chaoshan, respectively, for healthcare consumers. The monolingual healthcare providers perceived significant negative impacts of linguistic barriers on the entire healthcare delivery process (Ps < 0.0001). Regression analyses showed the length of stay in the Chaoshan region as a protective factor of linguistic barrier with a limited protective effect. CONCLUSIONS: This is the first report of significant linguistic barriers in healthcare imposed by Mandarin and Chaoshan dialects in Chaoshan, China. With perceived adverse impacts on the entire healthcare delivery and risks to the healthcare quality and burden, interventions such as professional interpreter service, service-learning interpreter program, or mobile interpreting apps that are medically accurate and culturally sensitive are suggested for dialectally diverse China.

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars.

BACKGROUND: Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Recent studies related have shown that competitive endogenous RNA (ceRNA) networks centering around miRNAs may play an influential role in HTS formation. This study aimed to construct and validate a three-miRNA (miR-422a, miR-2116-3p, and miR-3187-3p) ceRNA network, and explore its potential functions. METHODS: Quantitative real­time PCR (qRT­PCR) was used to compare expression levels of miRNAs, lncRNAs, and genes between HTS and normal skin. Target lncRNAs and genes of each miRNA were predicted using starBase as well as TargetScan database to construct a distinct ceRNA network; overlapping target lncRNAs and genes of the three miRNAs were utilized to develop a three-miRNA ceRNA network. For every network, protein-protein interaction (PPI) network analysis was performed to identify its hub genes. For each network and its hub genes, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to explore their possible functions. RESULTS: MiR-422a, miR-2116-3p, and miR-3187-3p were all downregulated in HTS tissues and fibroblasts. MiR-422a-based ceRNA network consisted of 101 lncRNAs with 133 genes; miR-2116-3p-centered ceRNA network comprised 85 lncRNAs and 978 genes; miR-3187-3p-derived ceRNA network encompassed 84 lncRNAs as well as 1128 genes. The three-miRNA ceRNA network included 2 lncRNAs with 9 genes, where MAPK1, FOSL2, ABI2, KPNA6, CBL, lncRNA-KCNQ1OT1, and lncRNA-EBLN3P were upregulated. According to GO and KEGG analysis, these networks were consistently related to ubiquitination. Three ubiquitination-related genes (CBL, SMURF2, and USP4) were upregulated and negatively correlated with the expression levels of the three miRNAs in HTS tissues. CONCLUSIONS: This study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.

Conditional survival after surgical resection of primary retroperitoneal tumors: a population-based study.

BACKGROUND: The purpose of this study was to assess conditional survival (CS) after resection of primary retroperitoneal tumors (RPTs). METHODS: The data of 1594 patients with primary RPTs who underwent surgery between 2004 and 2016 were retrieved from the Surveillance Epidemiology and End Results (SEER) database. Multivariate Cox analysis was used to identify prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS). CS was used to calculate the probability of survival for an additional 3 years after the patient had survived x years, according to the formulas: COS3 = OS (x + 3) /OS (x) and CCSS3 = CSS (x + 3)/CSS (x). RESULTS: The 1-, 3-, and 5-year OS rates of all patients were 89.8, 71.8, and 60.8%, while the 1-, 3-, and 5-year CSS rates were 91.9, 77.1, and 67.8%, respectively. Age, sex, FNCLCC grade, size, multifocality, histology, and chemotherapy were independent prognostic factors for OS and CSS. Among patients who survived for 1, 3, and 5 years, the COS3 rates were 72.9, 77.9, and 79.3%, and the CCSS3 rates were 78.1, 82.7, and 85.8%, respectively. Patients with poor clinicopathological characteristics achieved greater improvements in COS3 and CCSS3 rates, and the survival gaps between OS and COS3, as well as CSS and CCSS3 were more obvious. CONCLUSION: Postoperative CS of RPTs was dynamic and increased over time. CS increased more significantly in patients with poor clinicopathological characteristics.

Nanoribbon Superstructures of Graphene Nanocages for Efficient Electrocatalytic Hydrogen Evolution.

Two-dimensional carbon architectures are attracting tremendous interests for various promising applications due to their outstanding electronic and mechanical properties, although it is a great challenge to rationally devise facile and operative methodologies to engineer their structural traits owing to complex synthetic processes. Herein, for the first time, we fabricate two-dimensional carbon nanoribbons via direct thermal exfoliation of one-dimensional Ni-based metal-organic framework (MOF) nanorods, in which interconnected graphitic carbon nanocages are self-assembled into a belt-like superstructure with carbon-encapsulated Ni nanoparticles immobilized on the surface. Due to the unparalleled structural superiority, the MOF-derived carbon nanobelts exhibit excellent catalytic performances in electrocatalytic hydrogen evolution. Importantly, the practical synthetic strategy may trigger the rapid development of carbon-based superstructures in many frontier fields.

Ubiquitin-Specific Protease 15 Maintains Transforming Growth Factor-ß Pathway Activity by Deubiquitinating Transforming Growth Factor-ß Receptor I during Wound Healing.

Wound healing is a process of cutaneous barrier reconstruction that occurs after skin injury and involves diverse cytokines and cell types. Similar to several deubiquitinating enzymes, ubiquitin-specific protease 15 (USP15) can remove ubiquitin chains from specific proteins to rescue them from degradation. However, the regulatory role of USP15 in wound healing remains unclear. We investigated the dynamic function of USP15 in wound healing. First, in USP15 knockout mice, we observed a significant delay in wound closure. In addition, inhibition of cell proliferation and migration was observed in USP15-silenced human dermal fibroblasts. Through RNA sequencing, it was revealed that the transforming growth factor-ß (TGF-ß) pathway was suppressed after USP15 knockdown. Furthermore, coimmunoprecipitation demonstrated that USP15 could interact with TGF-ß receptor I and promote its deubiquitination, thereby maintaining TGF-ß signaling pathway activity by enhancing TGF-ß receptor I stability. These observations shed light on the function and mechanisms of USP15-mediated modulation of the TGF-ß signaling pathway during wound healing, thus providing a novel potential target for the treatment of refractory wounds.

Alisol A attenuates high-fat-diet-induced obesity and metabolic disorders via the AMPK/ACC/SREBP-1c pathway.

Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high-fat-diet-induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high-fat-diet-induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP-1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.