ABSTRACT
CRISPR-Cas9-mediated genome editing depends on PAM recognition to initiate DNA unwinding. PAM mutations can abolish Cas9 binding and prohibit editing. Here, we identified a Cas9 from the thermophile Alicyclobacillus tengchongensis for which the PAM interaction can be robustly regulated by DNA topology. AtCas9 has a relaxed PAM of N4CNNN and N4RNNA (R = A/G) and is able to bind but not cleave targets with mutated PAMs. When PAM-mutated DNA was in underwound topology, AtCas9 exhibited enhanced binding affinity and high cleavage activity. Mechanistically, AtCas9 has a unique loop motif, which docked into the DNA major groove, and this interaction can be regulated by DNA topology. More importantly, AtCas9 showed near-PAMless editing of supercoiled plasmid in E. coli. In mammalian cells, AtCas9 exhibited broad PAM preference to edit plasmid with up to 72% efficiency and effective base editing at four endogenous loci, representing a potentially powerful tool for near-PAMless editing.
Subject(s)
CRISPR-Cas Systems , Escherichia coli , Animals , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Editing , DNA/genetics , Plasmids , Mammals/metabolismABSTRACT
Inflammation plays an important role in the initiation and progression of colorectal cancer (CRC) and leads to ß-catenin accumulation in colitis-related CRC. However, the mechanism remains largely unknown. Here, pancreatic progenitor cell differentiation and proliferation factor (PPDPF) is found to be upregulated in CRC and significantly correlated with tumor-node-metastasis (TNM) stages and survival time. Knockout of PPDPF in the intestinal epithelium shortens crypts, decreases the number of stem cells, and inhibits the growth of organoids and the occurrence of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC. Mechanistically, PPDPF is found to interact with Casein kinase 1α (CK1α), thereby disrupting its binding to Axin, disassociating the ß-catenin destruction complex, decreasing the phosphorylation of ß-catenin, and activating the Wnt/ß-catenin pathway. Furthermore, interleukin 6 (IL6)/Janus kinase 2 (JAK2)-mediated inflammatory signals lead to phosphorylation of PPDPF at Tyr16 and Tyr17, stabilizing the protein. In summary, this study demonstrates that PPDPF is a key molecule in CRC carcinogenesis and progression that connects inflammatory signals to the Wnt/ß-catenin signaling pathway, providing a potential novel therapeutic target.
Subject(s)
Colorectal Neoplasms , Interleukin-6 , Humans , Interleukin-6/adverse effects , Interleukin-6/metabolism , Phosphorylation , beta Catenin/metabolism , Wnt Signaling Pathway , Janus Kinase 2/metabolism , Colorectal Neoplasms/genetics , Cell Proliferation , Cell Line, Tumor , Gene Expression Regulation, NeoplasticABSTRACT
Early research suggested that bone morphogenetic protein 10 (BMP10) is primarily involved in cardiac development and congenital heart disease processes. BMP10 is a newly identified cardiac-specific protein. In recent years, reports have emphasized the effects of BMP10 on myocardial apoptosis, fibrosis and immune response, as well as its synergistic effects with BMP9 in vascular endothelium and role in endothelial dysfunction. We believe that concentrating on this aspect of the study will enhance our knowledge of the pathogenesis of diabetes and the cardiovascular field. However, there have been no reports of any reviews discussing the role of BMP10 in diabetes and cardiovascular disease. In addition, the exact pathogenesis of diabetic cardiomyopathy is not fully understood, including myocardial energy metabolism disorders, microvascular changes, abnormal apoptosis of cardiomyocytes, collagen structural changes and myocardial fibrosis, all of which cause cardiac function impairment directly or indirectly and interact with one another. This review summarizes the research results of BMP10 in cardiac development, endothelial function and cardiovascular disease in an effort to generate new ideas for future research into diabetic cardiomyopathy.
Subject(s)
Bone Morphogenetic Proteins , Cardiovascular Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies , Humans , Animals , Bone Morphogenetic Proteins/metabolism , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/pathology , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , ApoptosisABSTRACT
Van der Waals (vdW)-layered materials have drawn tremendous interests due to their unique properties. Atom intercalation in the vdW gap of layered materials can tune their electronic structure and generate unexpected properties. Here a chemical-scissor-mediated method that enables metal intercalation into transition metal dichalcogenides (TMDCs) in molten salts is reported. By using this approach, various guest metal atoms (Mn, Fe, Co, Ni, Cu, and Ag) are intercalated into various TMDC hosts (such as TiS2 , NbS2 , TaS2 , TiSe2 , NbSe2 , TaSe2 , and Ti0.5 V0.5 S2 ). The structure of the intercalated compound and intercalation mechanism are investigated. The results indicate that the vdW gap and valence state of TMDCs can be modified through metal intercalation, and the intercalation behavior is dictated by the electron work function. The adjustable charge transfer and intercalation endow a channel for rapid mass transfer to enhance the electrochemical performances. Such a chemical-scissor-mediated intercalation provides an approach to tune the physical and chemical properties of TMDCs, which may open an avenue in functional application ranging from energy conversion to electronics.
ABSTRACT
The characteristics of solid electrolyte interphase (SEI) at both the cathode and anode interfaces are crucial for the performance of sodium-ion batteries (SIBs). The research demonstrates the merits of a balanced organic component, specifically the organic sodium alkyl sulfonate (ROSO2Na) featured in this work, in conjunction with the inorganic sodium fluoride (NaF), to enhance the interfacial stability. Using a customized electrolyte, it has optimized the interphase, curbing excess NaF production, and created a thin and uniform NaF/ROSO2Na-rich SEI layer. It offers exceptional protection against interface deterioration, transition metal dissolution, and concurrently ensures a consistent reduction in interfacial impedance. This creative approach results in a substantial improvement in the performance of both the Na0.9Ni0.4Fe0.2Mn0.4O2 cathode and the hard carbon anode. The cathode demonstrates remarkable average Coulombic efficiency exceeding 99.9% and a capacity retention of 81% after 500 cycles. Furthermore, the Ah-level pouch cell has shown outstanding performance with an 87% capacity retention after 400 cycles. Moving beyond the prevailing focus on inorganic-rich SEI, these results highlight the effectiveness of the customized organic-inorganic hybrid SEI formulation in improving SIB technology, offering an adaptable solution that ensures superior interfacial stability.
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The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.
ABSTRACT
The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVNVGlut2::MC4R and LCVGlut2::MC4R regulation of body weight, and axonal projections of LCVGlut2 neurons remain unclear. Conditional knockout of MC4R in chimeric mice was used to confirm the effects of VGlut2. Interscapular brown adipose tissue was injected with pseudorabies virus to study the central nervous system projections. We mapped the LCVGlut2 circuitry. Based on the Cre-LoxP recombination system, specific knockdown of MC4R in VGlut2 neurons resulted in weight gain in chimeric mice. Adeno-associated virus-mediated knockdown of MC4R expression in the PVN and LC had potential superimposed effects on weight gain, demonstrating the importance of VGlut2 neurons. Unlike these wide-ranging efferent projections, the PVN, hypothalamic arcuate nucleus, supraoptic nucleus of the lateral olfactory tegmental nuclei, and nucleus tractus solitarius send excitatory projections to LCVGlut2 neurons. The PVN â LC glutamatergic MC4R long-term neural circuit positively affected weight management and could help treat obesity.
Subject(s)
Paraventricular Hypothalamic Nucleus , Receptor, Melanocortin, Type 4 , Mice , Animals , Receptor, Melanocortin, Type 4/genetics , Receptor, Melanocortin, Type 4/metabolism , Body Weight , Paraventricular Hypothalamic Nucleus/metabolism , Neurons/metabolism , Weight GainABSTRACT
During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62â% for internal transcribed spacer (ITS), 98.66-99.10â% for ribosomal small subunit (nrSSU), and 96.36-98.22â% for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.
Subject(s)
Fatty Acids , Mucorales , Animals , Phylogeny , China , Sequence Analysis, DNA , Base Composition , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Bacterial Typing Techniques , Fatty Acids/chemistry , InvertebratesABSTRACT
The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of geneâenvironment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6â57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of geneâenvironment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.
Subject(s)
Gene-Environment Interaction , Keratoconus , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , China/epidemiology , Cohort Studies , Disease Progression , East Asian People/genetics , Keratoconus/genetics , Keratoconus/epidemiology , Longitudinal Studies , Prospective Studies , Surveys and QuestionnairesABSTRACT
BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.
Subject(s)
Anterior Eye Segment , Cornea , Corneal Topography , Myopia , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Male , Female , Adult , Myopia/diagnosis , Myopia/physiopathology , Corneal Topography/methods , Corneal Topography/instrumentation , Reproducibility of Results , Anterior Eye Segment/diagnostic imaging , Anterior Eye Segment/pathology , Young Adult , Cornea/diagnostic imaging , Cornea/pathology , Middle Aged , Biometry/methods , Adolescent , Prospective StudiesABSTRACT
INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.
Subject(s)
Cephalometry , Malocclusion, Angle Class II , Humans , Malocclusion, Angle Class II/therapy , Malocclusion, Angle Class II/diagnostic imaging , Adolescent , Male , Female , Orthodontic Appliance Design , Treatment Outcome , Tooth Movement Techniques/instrumentation , Tooth Movement Techniques/methods , Child , Mandible/pathology , Maxilla/pathology , Orthodontic Appliances, RemovableABSTRACT
Fusarium head blight (FHB), a devastating wheat disease caused by several species of Fusarium, threatens global wheat yield and quality (Erenstein et al. 2022). In August 2023, wheat spikes exhibiting clear FHB symptoms were observed in fields in Yunnan, China (24°16'46â³ N, 102°29'46â³ E), with an incidence rate of approximately 10%. Diseased wheat spikes exhibited a bleached, wilted appearance, with abundant orange sporodochia on the glumes, similar to previous reports (Osborne et al. 2007). Twenty-four symptomatic spikes were collected from a single field, and sporodochia were washed with sterile water to prepare a spore suspension of 1 × 10³ spores/ml, which was inoculated onto potato dextrose agar (PDA) to obtain monosporic cultures. Four reference strains (KUNCC 3418 to KUNCC 3420, and KUNCC 3431) were deposited at the Kunming Institute of Botany Culture Collection, Chinese Academy of Sciences (KUNCC). For species identification, four strains were cultured on PDA and carnation leaf agar (CLA) at 25°C, with incubation under a 12-hour near-UV light/dark cycle on CLA and in complete darkness for 24 hours on PDA. Colonies on PDA grew rapidly, appearing white and loosely flocculent. Abundant pale orange, translucent sporodochia formed on CLA. Sporodochial conidiogenous cells were monophialidic or polyphialidic, subulate to subcylindrical, 9.5-12 µm × 3-3.5 µm. Sporodochial macroconidia were naviculate to fusiform, with an elongate, tapering apical cell and a foot-shaped basal cell, 3-6-septate, 33-67.5 µm × 3.5-5.5 µm. The ITS, tef1-α, rpb1, rpb2, and cam regions were amplified and sequenced using primers ITS1/ITS4, EF-1/EF-2, rpb1-F7/G2R, rpb2-5F2/11aR, and CL1/CL2A, respectively (White et al. 1990; O'Donnell et al. 2000; O'Donnell et al. 2010; Reeb et al. 2004; O'Donnell et al. 1998). These sequences were deposited in GenBank for cam (PP951603 to PP951606), ITS (PP946846 to PP946849), tef-1α (PP719217, PP731572 to PP731574), rpb1 (PP719219, PP737839 to PP737841), and rpb2 (PP719218, PP951607 to PP951609). BLASTn analyses of these sequences showed an identity range of 99.7% to 100% with the epitype strain NRRL 36323 of F. compactum (GenBank: cam = GQ505560, ITS = MH855177, tef-1α = GQ505648, and rpb2 = GQ505826), with base pair matches of 663/665 bp for cam, 488/488 bp for ITS, 641/641 bp for tef-1α, and 892/892 bp for rpb2. Both morphological and BLASTn analyses confirmed these isolates as F. compactum (Leslie & Summerell 2006; Han et al. 2023). Pathogenicity tests were performed by spraying 1 ml of spore suspension (1 × 108 spores/ml) of F. compactum strains onto spikes of the wheat cultivar Yunmai 126 at the flowering stage (n = 9). Controls (n = 9) were treated only with sterile water. Following treatment, the wheat spikes were covered with plastic bags and incubated at 25°C for 10 days. After 14 days, the inoculated spikes turned bleached and dry, showing FHB symptoms, while the wheat spikes in the control treatment remained asymptomatic. The pathogenic fungus re-isolated from all diseased samples was confirmed as F. compactum. It has been frequently reported in association with crown and root rot of wheat, particularly in regions such as Turkey and Iran (Tunali et al. 2008; Besharati et al. 2017). To our knowledge, this is the first report of F. compactum on diseased wheat spikes in China. This finding provides valuable insights into the spread of F. compactum.
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Dynamic liquid level monitoring and measurement in oil wells is essential in ensuring the safe and efficient operation of oil extraction machinery and formulating rational extraction policies that enhance the productivity of oilfields. This paper presents an intelligent infrasound-based measurement method for oil wells' dynamic liquid levels; it is designed to address the challenges of conventional measurement methods, including high costs, low precision, low robustness and inadequate real-time performance. Firstly, a novel noise reduction algorithm is introduced to effectively mitigate both periodic and stochastic noise, thereby significantly improving the accuracy of dynamic liquid level detection. Additionally, leveraging the PyQT framework, a software platform for real-time dynamic liquid level monitoring is engineered, capable of generating liquid level profiles, computing the sound velocity and liquid depth and visualizing the monitoring data. To bolster the data storage and analytical capabilities, the system incorporates an around-the-clock unattended monitoring approach, utilizing Internet of Things (IoT) technology to facilitate the transmission of the collected dynamic liquid level data and computed results to the oilfield's central data repository via LoRa and 4G communication modules. Field trials on dynamic liquid level monitoring and measurement in oil wells demonstrate a measurement range of 600 m to 3000 m, with consistent and reliable results, fulfilling the requirements for oil well dynamic liquid level monitoring and measurement. This innovative system offers a new perspective and methodology for the computation and surveillance of dynamic liquid level depths.
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Exploiting novel materials with high specific capacities is crucial for the progress of advanced energy storage devices. Intentionally constructing functional heterostructures based on a variety of two-dimensional (2D) substances proves to be an extremely efficient method for capitalizing on the shared benefits of these materials. By elaborately designing the structure, a greatly escalated steadiness can be achieved throughout electrochemical cycles, along with boosted electron transfer kinetics. In this study, chemical vapor deposition (CVD) was utilized to alter the surface composition of multilayer Ti3C2Tx MXene, contributing to contriving various layered heterostructure materials through a precise adjustment of the reaction temperature. The optimal composite materials at a reaction temperature of 500 °C (defined as MX500), incorporating MXene as the conductive substrate, exhibited outstanding stability and high coulombic efficiency during electrochemical cycling. Meanwhile, the reactive sites are increased by using TiS2 and TiO2 at the heterogeneous interfaces, which sustains a specific capacity of 449 mAh g-1 after 200 cycles at a current density of 0.1 A g-1 and further demonstrates their exceptional electrochemical characteristics. Additionally, the noted pseudocapacitive properties, like MXene materials, further highlight the diverse capabilities of intuitive material design. This study illuminates the complex details of surface modification in multilayer MXene and offers a crucial understanding of the strategic creation of heterostructures, significantly impacting sophisticated electrochemical applications.
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Polyvictimization has received substantial scholarly attention globally since it has been put forward two decades ago. However, the current lack of understanding of the causes of polyvictimization hinders the design of intervention programs. This study aims to integrate social bonding theory and lifestyle-routine activity theory to understand the etiology of polyvictimization in the Chinese context. Our results suggest that social bonding exerted not only a direct effect on polyvictimization (ß = -.030, p < .001) but also an indirect effect through delinquency and association with delinquent peers. Surprisingly, we found that the pathways linking social bonding and polyvictimization do not differ across genders. Implications for practice and theories are discussed.
Subject(s)
Crime Victims , Juvenile Delinquency , Adolescent , Female , Humans , Male , Life Style , Risk-Taking , East Asian PeopleABSTRACT
OBJECTIVE: This study aimed to evaluate the biomechanical effects of aligner overtreatment on molar distalization using clear aligners. METHODS: Various models were created and integrated into finite-element software. Six distinct study models were devised for analysis. The first three models examined second molar distalization with different configurations of attachments, i.e. no attachment, horizontal or vertical attachment on the second molar. For the fourth and fifth models, Class II elastic traction, either implemented via a precision cut or button on canines, was applied. Lastly, aligner overtreatment with varying degrees of root distal tipping (0°, 2°, 4°, 6°, 8°, 10°, and 12°) for the second molar was designed in the last study model. RESULTS: Distalization of the second molar produced buccal tipping, distal tipping and intrusion of the second molar, and labial proclination and intrusion of the central incisor. These displacement tendencies were enhanced by adding attachments on the second molar, especially the vertical attachment. Class II elastic tractions enhanced molar distalization and diminish anchorage loss, with the precision-cut configuration being biomechanically superior to the button design. Aligner overtreatment produced bodily molar distalization and mitigated adverse biomechanical effects on anchorage teeth. LIMITATIONS: The study's limitations include the use of finite-element models, which may not fully represent real clinical scenarios, and the lack of consideration for individual patient variability. CONCLUSIONS: We suggest that Class II elastic traction via the precision-cut configuration and the design of vertical attachment on the second molar be applied for molar distalization. Appropriate aligner overtreatment helps achieve bodily molar distalization and minimizes adverse biomechanical effects on anchorage teeth.
Subject(s)
Finite Element Analysis , Molar , Tooth Movement Techniques , Humans , Tooth Movement Techniques/methods , Tooth Movement Techniques/instrumentation , Biomechanical Phenomena , Orthodontic Appliance Design , Orthodontic Anchorage Procedures/methods , Orthodontic Anchorage Procedures/instrumentation , Incisor , Cuspid , Computer Simulation , Dental Stress Analysis/methodsABSTRACT
BACKGROUND: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC. METHODS: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway. RESULTS: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007). CONCLUSIONS: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC.
Subject(s)
Carcinoma, Large Cell , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Phosphatidylinositol 3-Kinases/genetics , Exome/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Mutation , Lung Neoplasms/genetics , Lung Neoplasms/pathology , ErbB Receptors/genetics , LungABSTRACT
The volume expansion of CoFe2 O4 anode poses a significant challenge in the commercial application of lithium/sodium-ion batteries (LIBs/SIBs). However, metal-organic-frameworks (MOF) offer superior construction of heterostructures with refined interfacial interactions and lower ion diffusion barriers in Li/Na storage. In this study, the CoFe2 O4 @carbon nanofibers derived from MOF are produced through electrospinning, in situ growth followed by calcination, which are then confined within an MXene-confined MOF-derived porous CoFe2 O4 @carbon composite architecture under alkali treatment. The CoFe2 O4 nanofibers anchor on the alkalized MXene that is decorated with the NaOH solution to form a multi-pleated structure. The sandwich-like structure of the composite effectively alleviates the volume expansion and shortens the Li/Na-ion diffusion path, which displays high capacity and outstanding rate performance as anode materials for LIBs/SIBs. As a consequence, the obtained CoFe2 O4 @carbon@alkalized MXene composite anode shows satisfied rate performance at current density of 10 A g-1 for LIBs (318 mAh·g-1 ) and 5 A g-1 for SIBs (149 mAh g-1 ). The excellent cycling performance is further demonstrated at a high current density, where it maintains a discharge capacity of 807 mAh g-1 at 2 A g-1 after 400 cycles for LIBs and 130 mAh g-1 at 1 A g-1 even after 1000 cycles for SIBs.
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INTRODUCTION: The postoperative survival of oral squamous cell carcinoma (SCC) relies on precise detection and complete resection of original tumors. The mucosal extension of the tumor is evaluated visually during surgery, but small and flat foci are difficult to detect. Real-time fluorescence imaging may improve detection of tumor margins. MATERIALS AND METHODS: In the current study, a peptide-based near-infrared (NIR) fluorescence dye, c-MET-binding peptide-indocyanine green (cMBP-ICG), which specifically targets tumor via c-MET binding, was synthetized. A prospective pilot clinical trial then was conducted with oral SCC patients and intraoperatively to assess the feasibility of cMBP-ICG used to detect tumors margins. Fluorescence was histologically correlated to determine sensitivity and specificity. RESULTS: The immunohistochemistry (IHC) results demonstrated increased c-Met expression in oral SCC compared with normal mucosa. Tumor-to-background ratios ranged from 2.71 ± 0.7 to 3.11 ± 1.2 in different concentration groups. From 10 patients with oral SCC, 60 specimens were collected from tumor margins. The sensitivity and specificity of discriminative value derived from cMBP-ICG application in humans were respectively 100% and 75%. CONCLUSIONS: Topical application of cMBP-ICG is feasible and safe for optimizing intraoperative visualization and tumor margin detection in oral SCC patients, which could clinically increase the probability of complete resections and improve oncologic outcomes.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/surgery , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Squamous Cell Carcinoma of Head and Neck , Indocyanine Green , Fluorescent Dyes , Prospective Studies , PeptidesABSTRACT
Hydrogel-based flexible supercapacitors possess the merits of highly ionic conductivity and superior power density, but the existence of water limits their application in extreme temperature scenarios. Noticeably, it is a challenge for people to design more extremely temperature adaptable systems for flexible supercapacitors based on hydrogels with a wide temperature region. In this work, a wide-temperature flexible supercapacitor that can operate at -20-80 °C was fabricated by an organohydrogel electrolyte and its combined electrode (also known as an electrode/electrolyte composite). Upon introducing highly hydratable LiCl into an ethylene glycol (EG)/H2 O binary solvent, owing to the ionic hydration effect of LiCl and the hydrogen bond interaction between EG and H2 O molecules, the organohydrogel electrolyte exhibits satisfactory resistance to freezing (freezing point of -113.9 °C), anti-drying capability (78.2 % of weight retention after vacuum drying at 60 °C for 12â h) and excellent ionic conductivity both at room temperature (13.9â mS cm-1 ) and low temperature (6.5â mS cm-1 after 31â days at -20 °C). By using organohydrogel electrolyte as binder, the prepared electrode/electrolyte composite effectively reduces interface impedance and enhances specific capacitance due to the uninterrupted ion transport channels and extended interface contact area. The assembled supercapacitor delivers a specific capacitance of 149â F g-1 , a power density of 160â W kg-1 , and an energy density of 13.24â Wh kg-1 at a current density of 0.2â A g-1 . The initial 100 % capacitance can be maintained after 2000 cycles at 1.0â A g-1 . More importantly, the specific capacitances can be well maintained even at -20 and 80 °C. With other advantages such as excellent mechanical property, the supercapacitor is an ideal power source suitable for various working conditions.