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N6-methyladenosine (m6A) is a reversible mRNA modification that has been shown to play important roles in various biological processes. However, the roles of m6A modification in macrophages are still unknown. Here, we discover that ablation of Mettl3 in myeloid cells promotes tumour growth and metastasis in vivo. In contrast to wild-type mice, Mettl3-deficient mice show increased M1/M2-like tumour-associated macrophage and regulatory T cell infiltration into tumours. m6A sequencing reveals that loss of METTL3 impairs the YTHDF1-mediated translation of SPRED2, which enhances the activation of NF-kB and STAT3 through the ERK pathway, leading to increased tumour growth and metastasis. Furthermore, the therapeutic efficacy of PD-1 checkpoint blockade is attenuated in Mettl3-deficient mice, identifying METTL3 as a potential therapeutic target for tumour immunotherapy. N6-methyladenosine (m6A) is a reversible mRNA modification with important roles in cancer biology and immunoregulation. Here, the authors show that myeloid-specific deletion of Mettl3, the catalytic subunit of the methyltransferase complex, promotes tumor growth and metastasis in preclinical tumor models, influencing macrophage reprogramming and attenuating PD-1 blockade.

HighlightsDendrite-free stable Zn plating/stripping was achieved for over 500 h at 2 mA cm−2.No short-circuit for 10 mAh cm−2 of Zn plating.Zn|MnO2 cells delivered nearly 100% capacity retention over 2000 cycles.Owing to the merits of low cost, high safety and environmental benignity, rechargeable aqueous Zn-based batteries (ZBs) have gained tremendous attention in recent years. Nevertheless, the poor reversibility of Zn anodes that originates from dendrite growth, surface passivation and corrosion, severely hinders the further development of ZBs. To tackle these issues, here we report a Janus separator based on a Zn-ion conductive metal–organic framework (MOF) and reduced graphene oxide (rGO), which is able to regulate uniform Zn2+ flux and electron conduction simultaneously during battery operation. Facilitated by the MOF/rGO bifunctional interlayers, the Zn anodes demonstrate stable plating/stripping behavior (over 500 h at 1 mA cm−2), high Coulombic efficiency (99.2% at 2 mA cm−2 after 100 cycles) and reduced redox barrier. Moreover, it is also found that the Zn corrosion can be effectively retarded through diminishing the potential discrepancy on Zn surface. Such a separator engineering also saliently promotes the overall performance of Zn|MnO2 full cells, which deliver nearly 100% capacity retention after 2000 cycles at 4 A g−1 and high power density over 10 kW kg−1. This work provides a feasible route to the high-performance Zn anodes for ZBs.

The polysaccharides isolated and purified from different parts of the medicinal fungus Cordyceps cicadae were identified, and three extracts displaying significant biological activities were selected for further study. The bacterium substance polysaccharides (BSP), spore powder polysaccharides (SPP), and pure powder polysaccharides (PPP) were separated, purified, and collected from the sclerotia, spores, and fruiting bodies of Cordyceps cicadae, respectively. The structures of Cordyceps cicadae polysaccharides were analyzed using gas chromatography, Fourier-transform infrared spectroscopy, methylation analysis, and one-dimensional (1H and 13C) nuclear magnetic resonance spectroscopy. Moreover, the hypoglycemic effect of Cordyceps cicadae polysaccharides was examined in both in vitro and in vivo models. BSP, SPP, and PPP significantly increased glucose absorption in HepG2 cells, and alleviated insulin resistance (IR) in the in vitro model. SPP was the most effective, and was therefore selected for further study of its hypoglycemic effect in vivo. SPP effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. SPP regulated the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway. The hypoglycemic mechanism of SPP may reduce hepatic insulin resistance by activating the PI3K/Akt signaling pathway. Spore powder polysaccharides (SPP) extracted from Cordyceps cicadae effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. The mechanism underlying the hypoglycemic effect of SPP regulates the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway to alleviate insulin resistance. Our results provide a theoretical basis for research into the hypoglycemic effect of Cordyceps cicadae, and lay the foundation for the development of functional products.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, insulin resistance (IR) and dyslipidaemia. Consumption of a high-fat diet (HFD) enriched in SFA leads to the accumulation of ceramide (Cer), the central molecule in sphingolipid metabolism. Elevations in plasma and tissue Cer are found in obese individuals, and there is evidence to suggest that Cer lipotoxicity contributes to the MetS. EPA and DHA have shown to improve MetS parameters including IR, inflammation and hypertriacylglycerolaemia; however, whether these improvements are related to Cer is currently unknown. This review examines the potential of EPA and DHA to improve Cer lipotoxicity and MetS parameters including IR, inflammation and dyslipidaemia in vitro and in vivo. Current evidence from cell culture and animal studies indicates that EPA and DHA attenuate palmitate- or HFD-induced Cer lipotoxicity and IR, whereas evidence in humans is greatly lacking. Overall, there is intriguing potential for EPA and DHA to improve Cer lipotoxicity and related MetS parameters, but more research is warranted.

On 31 December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, China, and caused the outbreak of the Coronavirus Disease 2019 (COVID-19). To date, computed tomography (CT) findings have been recommended as major evidence for the clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the imaging characteristics and changes throughout the disease course in patients with COVID-19 in order to provide some help for clinicians. Typical CT findings included bilateral ground-glass opacity, pulmonary consolidation, and prominent distribution in the posterior and peripheral parts of the lungs. This review also provides a comparison between COVID-19 and other diseases that have similar CT findings. Since most patients with COVID-19 infection share typical imaging features, radiological examinations have an irreplaceable role in screening, diagnosis and monitoring treatment effects in clinical practice.

Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remains mostly elusive. Here, we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii . The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may facilitate the release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the Q B site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b 559 , potentially fulfilling a photoprotective role by preventing the generation of reactive oxygen species. Here the authors show an intermediate state of the photosystem II (PSII) repair cycle, where three protein factors and an α-tocopherol quinone molecule are associated with a damaged PSII at distinct sites, fulfilling their specific functions in the repair process.

Sorption thermal energy storage is pivotal for enhancing renewable energy utilization and supporting the transition to carbon neutrality. Its performance hinges on the formation and dynamic evolution of the reaction zone. However, the lack of in situ, spatially resolved measurement tools has hampered a mechanistic understanding and rational design. To address this, this study presents a method for characterizing the reaction zone dynamics through high-resolution intra-reactor temperature profiling. Applying this method to a zeolite 13X packed-bed reactor, we establish, for the first time, quantitative empirical correlations between operating parameters and these intrinsic reaction zone properties. A key finding is that the stable duration and output temperature are governed by the length, propagation velocity, and exothermic area of the reaction zone, coupled with the total sorption heat. Furthermore, the effects of the four critical operational parameters, including inlet air temperature, relative humidity, airflow rate, and packing thickness, on both the reaction zone characteristics and thermal output performances were systematically investigated. By integrating these mechanistic insights, we propose a hierarchical control strategy and actionable application guidelines to tailor the thermal output on demand.

Background Among autoimmune encephalitis (AE), anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type. In patients with anti-NMDAR encephalitis, psychiatric and cognitive symptoms were often observed as the initial manifestations, whereas cerebellar ataxia was rarely reported. Case presentation We report the case of a 22-year-old male patient who initially presented with cerebellar ataxia and was eventually diagnosed with anti-NMDAR encephalitis on the basis of positive results for anti-NMDAR antibodies in the cerebrospinal fluid. After combined therapy with intravenous immunoglobulin, methylprednisolone, and rituximab and subsequent rehabilitation, the patient’s symptoms were gradually alleviated. Conclusions This case highlights the atypical presentation of anti-NMDAR encephalitis with cerebellar ataxia as the initial symptom, which is rare. Granule cell dysfunction, due to the wide distribution of GluN1 subunits, may disrupt the signaling to Purkinje cells, resulting in ataxia. Early recognition and treatment with immunotherapy, followed by rehabilitation, are crucial for improving patient outcomes, especially in cases with atypical presentations.

S-parameters are widely used to detail the scattering parameters of radio frequency (RF) components and microwave circuit modules. The vector network analyzer (VNA) is the most commonly used device for measuring S-parameters. Given the multiple frequency points, complex values, and intricate uncertainty propagation involved, accurately assessing the uncertainty of S-parameter measurements is difficult. In this study, we proposed a new method for assessing S-parameter uncertainty based on the covariance matrices, tracing back to the nominal uncertainty of calibration standards. First, we analyzed the relevant theory of uncertainty assessment using covariance matrices and subsequently deduced the mechanism of Type B uncertainty propagating from calibration standards to error model coefficients and S-parameter measurements to evaluate Type B measurement uncertainty. In this study, a novel measurement system was constructed for measuring grounded coplanar waveguides by using a VNA and calibration standards with 8- and 12-error models. Initially, the model assessed the Type B uncertainty of measuring four S-parameters of a grounded coplanar waveguide. Next, the VNA calibrated with the 12-error model was used to conduct multiple repeated measurements to assess the Type A uncertainty of the grounded coplanar waveguide. Finally, the composite uncertainty was constructed, which demonstrated that the proposed method can be used for assessing the uncertainty of S-parameters.

Alzheimer’s disease (AD) is a heterogeneous disease with complex clinicopathological characteristics. To date, the role of m6A RNA methylation in monocyte-derived macrophages involved in the progression of AD is unknown. In our study, we found that methyltransferase-like 3 (METTL3) deficiency in monocyte-derived macrophages improved cognitive function in an amyloid beta (Aβ)-induced AD mouse model. The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in DNA methyltransferase 3A ( Dnmt3a ) mRNAs and consequently impaired YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of alpha-tubulin acetyltransferase 1 ( Atat1 ) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of α-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Aβ clearance, which led to the alleviated symptoms of AD. Collectively, our findings demonstrate that m6A methylation could be a promising target for the treatment of AD in the future.