N6-methyladenosine (m6A) methyltransferase Mettl3 is involved in conventional T cell immunity; however, its role in innate immune cells remains largely unknown. Here, we show that Mettl3 ...intrinsically regulates invariant natural killer T (iNKT) cell development and function in an m6A-dependent manner. Conditional ablation of Mettl3 in CD4+CD8+ double-positive (DP) thymocytes impairs iNKT cell proliferation, differentiation, and cytokine secretion, which synergistically causes defects in B16F10 melanoma resistance. Transcriptomic and epi-transcriptomic analyses reveal that Mettl3 deficiency disturbs the expression of iNKT cell-related genes with altered m6A modification. Strikingly, Mettl3 modulates the stability of the Creb1 transcript, which in turn controls the protein and phosphorylation levels of Creb1. Furthermore, conditional targeting of Creb1 in DP thymocytes results in similar phenotypes of iNKT cells lacking Mettl3. Importantly, ectopic expression of Creb1 largely rectifies such developmental defects in Mettl3-deficient iNKT cells. These findings reveal that the Mettl3-m6A-Creb1 axis plays critical roles in regulating iNKT cells at the post-transcriptional layer.
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•Mettl3-dependent m6A methylation plays a key role in iNKT cell development•A comprehensive m6A landscape of low-input iNKT cells is established by m6A-LACE-seq•Mettl3 deficiency disrupts iNKT cell-related gene network in an m6A-dependent manner•The Mettl3-m6A-Creb1 axis is critical for sustaining iNKT cell differentiation and function
You et al. demonstrate that Mettl3 is essential for regulating iNKT cell proliferation, differentiation, and melanoma resistance. The study highlights the critical role of Mettl3-dependent m6A modification in controlling iNKT cell-related gene expression, particularly in maintaining the stability of Creb1 and c-Myc transcripts.
N
-methyladenosine (m
A) methyltransferase Mettl3 is involved in conventional T cell immunity; however, its role in innate immune cells remains largely unknown. Here, we show that Mettl3 ...intrinsically regulates invariant natural killer T (iNKT) cell development and function in an m
A-dependent manner. Conditional ablation of Mettl3 in CD4
CD8
double-positive (DP) thymocytes impairs iNKT cell proliferation, differentiation, and cytokine secretion, which synergistically causes defects in B16F10 melanoma resistance. Transcriptomic and epi-transcriptomic analyses reveal that Mettl3 deficiency disturbs the expression of iNKT cell-related genes with altered m
A modification. Strikingly, Mettl3 modulates the stability of the Creb1 transcript, which in turn controls the protein and phosphorylation levels of Creb1. Furthermore, conditional targeting of Creb1 in DP thymocytes results in similar phenotypes of iNKT cells lacking Mettl3. Importantly, ectopic expression of Creb1 largely rectifies such developmental defects in Mettl3-deficient iNKT cells. These findings reveal that the Mettl3-m
A-Creb1 axis plays critical roles in regulating iNKT cells at the post-transcriptional layer.
Exfoliated black phosphorus (BP), as a monolayer or few-layer material, has attracted tremendous attention owing to its unique physical properties for applications ranging from optoelectronics to ...photocatalytic hydrogen production. Approaching intrinsic properties has been, however, challenged by chemical reactions and structure degradation of BP under ambient conditions. Surface passivation by capping agents has been proposed to extend the processing time window, yet contamination or structure damage rise challenges for BP applications. Here, we report experiments combined with first-principle calculations that address the degradation chemistry of BP. Our results show that BP reacts with oxygen in water even without light illumination. The reaction follows a pseudo-first-order parallel reaction kinetics, produces PO2 3–, PO3 3–, and PO4 3– with reaction rate constants of 0.019, 0.034, and 0.023 per day, respectively, and occurs preferentially from the P atoms locating at BP edges, which yields structural decay from the nanoflake edges in water. In addition, a negligible decay ratio (0.9 ± 0.3 mol %) and preserved photocatalytic activity of BP are observed after storage in deoxygenated water for 15 days without surface passivation under ambient light. Our results reveal the chemistry of BP degradation and provide a practical approach for exfoliation, delivery, and application of BP.
Osteoarthritis (OA), a disabling joint inflammatory disease, is characterized by the progressive destruction of cartilage, subchondral bone remodeling, and chronic synovitis. Due to the prolongation ...of the human lifespan, OA has become a serious public health problem that deserves wide attention. The development of OA is related to numerous factors. Among the factors, nitric oxide (NO) plays a key role in mediating this process. NO is a small gaseous molecule that is widely distributed in the human body, and its synthesis is dependent on NO synthase (NOS). NO plays an important role in various physiological processes such as the regulation of blood volume and nerve conduction. Notably, NO acts as a double-edged sword in inflammatory diseases. Recent studies have shown that NO and its redox derivatives might be closely related to both normal and pathophysiological joint conditions. They can play vital roles as normal bone cell-conditioning agents for osteoclasts, osteoblasts, and chondrocytes. Moreover, they can also induce cartilage catabolism and cell apoptosis. Based on different conditions, the NO/NOS system can act as an anti-inflammatory or pro-inflammatory agent for OA. This review summarizes the studies related to the effects of NO on all normal and OA joints as well as the possible new treatment strategies targeting the NO/NOS system.
Gas–liquid coalescence filters are extensively applied in industrial fields, mainly to separate oil mist droplets that are carried in gases. The traditional wettability treatment on the filter ...surface can improve the filtration efficiency but usually also increases the pressure drop. In this study, a surface modification method based on tip patterns was proposed. Nonuniform wettability filter surfaces with tip patterns were prepared by combining star-shaped molds and spraying modification to explore the influence of key pattern parameters on the performance of filters. In this way, industrial cartridges were prepared based on the optimal modification parameters and their filtration performance was analyzed and verified. The results showed that liquid collection by the modified filters improved significantly under the combined effect of the wettability driving force and Laplace force produced by the shape gradient, while the steady-state pressure drop decreased by 34.2–47.4% compared to the substrate filter. The modifications facilitated an increase in the effective fiber surface area and strengthened the droplet capture effect by diffusion. When the tip angle was 50°, all of the modified filters achieved the highest droplet filtration efficiency across different droplet size intervals. When there were nine patterns at a 50° tip angle, the modified filters achieved the optimal comprehensive filtration performance, and the steady-state quality factor increased 3.1- and 3.4-fold for submicrometer and micrometer droplets, respectively, compared to the substrate filter. Industrial cartridges were prepared based on the optimal filters. Under different liquid-loading rates, the modified cartridges had significantly higher efficiency and lower resistance compared to the unmodified cartridge. The proposed pattern modification method provides a direction for the design and development of new high-performance coalescence components.
Adolescent health risk behaviors are a public health priority given their prevalence and their associations with chronic diseases and life quality in adulthood. This study examined the heterogeneity ...of adolescent health risk behaviors and the associations between demographic characteristics and subgroup membership in rural western China.
In fall 2015, 2805 students from rural middle schools in Sichuan Province were surveyed using the Health-Related Behavior Questionnaire for Adolescents. Latent class analysis (LCA) was used to identify subgroups of adolescents with distinct patterns of health risk behaviors. Differences in class membership related to selected demographic characteristics were examined using multinomial logistic regression analysis.
A four-class model emerged: (1) high-risk group (n = 108, 4.0%), (2) high-physical-inactivity and suicide-risk group (n = 340, 12.1%), (3) moderate-risk group (n = 897, 32.0%), and (4) low-risk group (n = 1460, 52.1%). The multinomial logistic regression analysis revealed that boys and adolescents with poor parental relationships and high allowances (spending money) were significantly more likely to be in the high-risk group than the low-risk group.
Adolescents in rural western China are a heterogeneous population requiring different tailored and effective interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The stator structure is one of the main factors affecting the electromagnetic performance of permanent magnet (PM) motors. In this paper, an in-depth study and analysis of how to reduce the cogging ...torque is carried out from the perspective of the stator structure. According to the theory of cogging torque synthesis, this paper presents a unified calculation formula for different PM motor skewed notch designs. This theory is verified with a 20-pole, 60-slot motor and a 20-pole, 24-slot motor, respectively. The formula worked out proved to be highly applicable. The formula is intended to address how to quickly obtain key data (skew angle, notch depth) in a skewed notch study.
Abstract
Post-surgical treatments of the human throat often require continuous monitoring of diverse vital and muscle activities. However, wireless, continuous monitoring and analysis of these ...activities directly from the throat skin have not been developed. Here, we report the design and validation of a fully integrated standalone stretchable device platform that provides wireless measurements and machine learning-based analysis of diverse vibrations and muscle electrical activities from the throat. We demonstrate that the modified composite hydrogel with low contact impedance and reduced adhesion provides high-quality long-term monitoring of local muscle electrical signals. We show that the integrated triaxial broad-band accelerometer also measures large body movements and subtle physiological activities/vibrations. We find that the combined data processed by a 2D-like sequential feature extractor with fully connected neurons facilitates the classification of various motion/speech features at a high accuracy of over 90%, which adapts to the data with noise from motion artifacts or the data from new human subjects. The resulting standalone stretchable device with wireless monitoring and machine learning-based processing capabilities paves the way to design and apply wearable skin-interfaced systems for the remote monitoring and treatment evaluation of various diseases.
Engineering phosphorous anodes
A focus of battery research has been the development of a range of lithium, sodium, and potassium cathodes, but improving anode materials is also an important goal. ...Silicon has shown some promise for replacing graphite because of its exceptional capacity, but the dramatic volume change during lithiation-delithiation processes often leads to failure. Jin
et al.
developed a composite that is made of black phosphorous and graphite in its core and covered with swollen polyaniline. In contrast to previous efforts, bonding between the carbon and phosphorous allows for a high charging rate without sacrifices in capacity and cycling stability.
Science
, this issue p.
192
Black phosphorus composites with engineered interfaces deliver high capacity, high rate capability, and long cycle life.
High-rate lithium (Li) ion batteries that can be charged in minutes and store enough energy for a 350-mile driving range are highly desired for all-electric vehicles. A high charging rate usually leads to sacrifices in capacity and cycling stability. We report use of black phosphorus (BP) as the active anode for high-rate, high-capacity Li storage. The formation of covalent bonds with graphitic carbon restrains edge reconstruction in layered BP particles to ensure open edges for fast Li
+
entry; the coating of the covalently bonded BP-graphite particles with electrolyte-swollen polyaniline yields a stable solid–electrolyte interphase and inhibits the continuous growth of poorly conducting Li fluorides and carbonates to ensure efficient Li
+
transport. The resultant composite anode demonstrates an excellent combination of capacity, rate, and cycling endurance.
The usage of flame retardants in flammable polymers has been an effective way to protect both lives and material goods from accidental fires. Phosphorus flame retardants have the potential to be ...follow-on flame retardants after halogenated variants, because of their low toxicity, high efficiency and compatibility. Recently, the emerging allotrope of phosphorus, two-dimensional black phosphorus, as a flame retardant has been developed. To further understand its performance in flame-retardant efficiency among phosphorus flame retardants, in this work, we built model materials to compare the flame-retardant performances of few-layer black phosphorus, red phosphorus nanoparticles, and triphenyl phosphate as flame-retardant additives in cellulose and polyacrylonitrile. Aside from the superior flame retardancy in polyacrylonitrile, few-layer black phosphorus in cellulose showed the superior flame-retardant efficiency in self-extinguishing, ~1.8 and ~4.4 times that of red phosphorus nanoparticles and triphenyl phosphate with similar lateral size and mass load (2.5~4.8 wt%), respectively. The char layer in cellulose coated with the few-layer black phosphorus after combustion was more continuous and smoother than that with red phosphorus nanoparticles, triphenyl phosphate and blank, and the amount of residues of cellulose coated with the few-layer black phosphorus in thermogravimetric analysis were 10 wt%, 14 wt% and 14 wt% more than that with red phosphorus nanoparticles, triphenyl phosphate and blank, respectively. In addition, although exothermic reactions, the combustion enthalpy changes in the few-layer black phosphorus (-127.1 kJ mol
) are one third of that of red phosphorus nanoparticles (-381.3 kJ mol
). Based on a joint thermodynamic, spectroscopic, and microscopic analysis, the superior flame retardancy of the few-layer black phosphorus was attributed to superior combustion reaction suppression from the two-dimensional structure and thermal nature of the few-layer black phosphorus.
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