NSUN5/TET2-directed chromatin-associated RNA modification of 5-methylcytosine to 5-hydroxymethylcytosine governs glioma immune evasion.

Malignant glioma exhibits immune evasion characterized by highly expressing the immune checkpoint CD47. RNA 5-methylcytosine(m5C) modification plays a pivotal role in tumor pathogenesis. However, the mechanism underlying m5C-modified RNA metabolism remains unclear, as does the contribution of m5C-modified RNA to the glioma immune microenvironment. In this study, we demonstrate that the canonical 28SrRNA methyltransferase NSUN5 down-regulates ß-catenin by promoting the degradation of its mRNA, leading to enhanced phagocytosis of tumor-associated macrophages (TAMs). Specifically, the NSUN5-induced suppression of ß-catenin relies on its methyltransferase activity mediated by cysteine 359 (C359) and is not influenced by its localization in the nucleolus. Intriguingly, NSUN5 directly interacts with and deposits m5C on CTNNB1 caRNA (chromatin-associated RNA). NSUN5-induced recruitment of TET2 to chromatin is independent of its methyltransferase activity. The m5C modification on caRNA is subsequently oxidized into 5-hydroxymethylcytosine (5hmC) by TET2, which is dependent on its binding affinity for Fe2+ and α-KG. Furthermore, NSUN5 enhances the chromatin recruitment of RBFOX2 which acts as a 5hmC-specific reader to recognize and facilitate the degradation of 5hmC caRNA. Notably, hmeRIP-seq analysis reveals numerous mRNA substrates of NSUN5 that potentially undergo this mode of metabolism. In addition, NSUN5 is epigenetically suppressed by DNA methylation and is negatively correlated with IDH1-R132H mutation in glioma patients. Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.

High expression of VTA1 is an adverse prognostic factor in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common pathological type of non-small cell lung cancer; identifying preferable biomarkers has become one of the current challenges. Given that VTA1 has been reported associated with tumor progression in various human solid cancers but rarely reported in LUAD, herein, RNA sequencing data from TCGA and GTEx were obtained for analysis of VTA1 expression and differentially expressed gene (DEG). Furthermore, functional enrichment analysis of VTA1-related DEGs was performed by GO/KEGG, GSEA, immune cell infiltration analysis, and protein-protein interaction (PPI) network. In addition, the clinical significance of VTA1 in LUAD was figured out by Kaplan-Meier Cox regression and prognostic nomogram model. R package was used to analyze incorporated studies. As a result, VTA1 was highly expressed in various malignancies, including LUAD, compared with normal samples. Moreover, high expression of VTA1 was associated with poor prognosis in 533 LUAD samples, as well as T stage T2&T3&T4, N stage N1&N2&N3, M stage M1, pathologic stage II&III&IV, and residual tumor R1&R2, et al. (P < 0.05). High VTA1 was an independent prognostic factor in Cox regression analysis; Age and cytogenetics risk were included in the nomogram prognostic model. Furthermore, a total of 4232 DEGs were identified between the high- and the low-expression group, of which 736 genes were up-regulated and 3496 genes were down-regulated. Collectively, high expression of VTA1 is a potential biomarker for adverse outcomes in LUAD. The DEGs and pathways recognized in the study provide a preliminary grasp of the underlying molecular mechanisms of LUAD carcinogenesis and progression.

Increasing the organic loading rate of household food waste anaerobic digestion by landfill leachate addition: Performance and mechanism.

A high amount of easily degradable organics and the absence of trace metals (TMs) in household food waste (HFW) lowered the stability and efficiency of anaerobic digestion (AD) of HFW. Leachate addition to the AD of HFW can provide ammonia nitrogen and TMs to address the accumulation of volatile fatty acids and the lack of TMs. To study the effect of leachate addition on increasing organic loading rate (OLR), both mono-digestion of HFW and AD of HFW with leachate addition were evaluated using two continuously stirred tank reactors. The OLR of the mono-digestion reactor only reached 2.5 g COD/L/d. However, with the addition of ammonia nitrogen and TMs, the OLR of the failed mono-digestion reactor increased by 2 and 3.5 g COD/L/d, respectively. The specific methanogenic activity increased by 94.4% and the hydrolysis efficiency increased by 135%. Finally, the OLR of mono-digestion of HFW reached 8 g COD/L/d, with a hydraulic retention time (HRT) of 8 days and methane production rate of 2.4 L/L/d. In the leachate addition reactor, the OLR reached 15 g COD/L/d, while the HRT and methane production were 7 days and 3.4 L/L/d, respectively. This study demonstrates that leachate addition substantially improves the AD efficiency of HFW. The two main mechanisms of increasing the OLR of an AD reactor are the buffer capacity of ammonia nitrogen and the stimulation of methanogen by TMs from leachate.

Enhancing the nonreciprocal Goos-Hänchen shift by the Fano resonance of coupled gyromagnetic chains at normal incidence.

We report a resonance-enhanced nonreciprocal Goos-Hänchen (GH) shift for the wave reflected from the coupled gyromagnetic chains. We demonstrate that the Fano resonance enhances the GH shift with high reflectivity at normal incidence, and the resonance results from the interference between the leaky guided modes of the coupled chains. Furthermore, we show that the GH shift can be controlled by the number of stacked chains. The Fano resonance-enhanced GH shift offers a new efficiently way to enhance and control the GH shift for reflected wave beam. Such coupled gyromagnetic chains provide an extremely compact way for the devices such as unidirectional couplers and other integration photonic components, paving the way for the applications of nonreciprocal GH shift.

Roles of extracellular vesicles in periodontal homeostasis and their therapeutic potential.

Periodontal tissue is a highly dynamic and frequently stimulated area where homeostasis is easily destroyed, leading to proinflammatory periodontal diseases. Bacteria-bacteria and cell-bacteria interactions play pivotal roles in periodontal homeostasis and disease progression. Several reviews have comprehensively summarized the roles of bacteria and stem cells in periodontal homeostasis. However, they did not describe the roles of extracellular vesicles (EVs) from bacteria and cells. As communication mediators evolutionarily conserved from bacteria to eukaryotic cells, EVs secreted by bacteria or cells can mediate interactions between bacteria and their hosts, thereby offering great promise for the maintenance of periodontal homeostasis. This review offers an overview of EV biogenesis, the effects of EVs on periodontal homeostasis, and recent advances in EV-based periodontal regenerative strategies. Specifically, we document the pathogenic roles of bacteria-derived EVs (BEVs) in periodontal dyshomeostasis, focusing on plaque biofilm formation, immune evasion, inflammatory pathway activation and tissue destruction. Moreover, we summarize recent advancements in cell-derived EVs (CEVs) in periodontal homeostasis, emphasizing the multifunctional biological effects of CEVs on periodontal tissue regeneration. Finally, we discuss future challenges and practical perspectives for the clinical translation of EV-based therapies for periodontitis.

Network pharmacology and experimental evidence reveal the protective mechanism of Yi-Qi Cong-Ming decoction on age-related hearing loss.

CONTEXT: Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly. OBJECTIVE: To explore the mechanism of YQCM decoction in the treatment of ARHL. MATERIALS AND METHODS: The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and an in vitro model of ARHL by exposing auditory cells with 100 µM H2O2 for 3 h were applied. Cell viability and mitochondrial membrane potential (ΔΨM) were detected by CCK-8 and high-content analysis. γH2AX and cleaved caspase-3 were detected by Western blot. RESULTS: The main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. H2O2 treatment could reduce the cell viability by 68% and impaired ΔΨM, while 90 µg/mL YQCM pre-treatment could restore the cell viability by 97.45% and increase ΔΨM (2-fold higher). YQCM pre-treatment also reduced γH2AX and cleaved caspase-3 protein levels. CONCLUSIONS: Our study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL.

Broadband trifunctional metasurface and its application in a lens antenna.

Multifunctional metasurfaces have attracted extensive attention due to their ability to achieve diversified wavefront controls in flat devices. To date, most designs through metasurface are confined to realize one or two functionalities. In this work, we implement a broadband trifunctional metasurface by using different meta-atoms of the same type. The meta-atoms can independently manipulate the amplitude and phase of transmitted waves and the phase of reflected waves in a wide frequency range. Thus, they help the metasurface achieving the functionalities of beam deflection, diffuse scattering, and beam focusing according to the polarization and the direction of incident waves. The metasurface is applied to a metalens antenna, which features broadband, low side-lobe, and stealth. The metalens antenna works at the frequency range 9.8 GHz to 11.6 GHz with gain over 25 dBi. Experiments verify the functions of the trifunctional metasurface and are in good agreement with the designs. Our approach provides a solid platform for high-efficiency wideband metadevices with diverse functionalities.

Broadband radar cross section reduction by an absorptive metasurface based on a magnetic absorbing material.

A highly feasible approach to achieve a broadband radar cross section (RCS) reduction using a simple magnetic metasurface is presented. A magnetic absorbing material (MAM) with high permittivity and magnetic loss is introduced into the metasurface design instead of the more common dielectric material to considerably reduce its thickness. The metasurface is composed of an optimized two-dimensional array of MAM meta-atoms and a metal plate in back. The meta-atoms share a simple square ring shape but with variable geometrical parameters, forming strong absorption in different frequency bands with large reflection phase differences. By hybridizing the absorption and phase-cancelation technique, a 10-dB RCS reduction from 3.4 to 18 GHz is achieved at a thickness of only 4 mm. Further experimental measurements are provided to evaluate the performance. Our work provides a promising way to broaden the bandwidth of RCS reduction with low density, reduced thickness, and stable performance, which can be utilized in harsh physical and chemical environments.

Invisible Gateway by Superscattering Effect of Metamaterials.

Illusion devices, such as superscatterer and invisible gateway, have been theoretically studied under the theory of transformation optics and folded geometry transformations. The realization of these devices needs building blocks of metamaterials with negative permittivities and permeabilities. However, superscattering effects, such as stopping wave propagation in an air channel, have not been verified from illusion devices physically because of the challenge of metamaterial design, fabrication, and material loss. In this Letter, we implement a big metamaterial superscatterer, and experimentally demonstrate its superscattering effect at microwave frequencies by field-mapping technology. We confirm that superscattering is originated from the excitation of surface plasmons. Integrated with superscatterer, we experimentally display that an invisible gateway could stop electromagnetic waves in an air channel with a width much larger than the cutoff width of the corresponding rectangular waveguide. Our results provide a first direct observation of superscattering effect of double negative metamaterials and invisible gateway for electromagnetic waves. It builds up an ideal platform for future designs of other illusion devices.

Effect of ¹³¹I Therapy on Complete Blood Count in Patients with Differentiated Thyroid Cancer.

BACKGROUND The aim of this study was to investigate the effects of ¹³¹I therapy on complete blood count (CBC) in patients with differentiated thyroid cancer (DTC). MATERIAL AND METHODS We analyzed CBC in 542 patients with DTC who were grouped according to treatment cycles and cumulative dose and then subdivided by sex and age. The effects of ¹³¹I therapy among the different groups and subgroups were analyzed. RESULTS After sorting patients by treatment cycles and doses, ¹³¹I therapy was found to have different effects on CBC depending on patient sex and age. The effect on white blood cell (WBC) counts persisted longer in women, while increases in hemoglobin (Hb) were more significant in men. The influence on red blood cell (RBC) counts was short-lived in patients aged 45 to 54 years. Monocyte counts were significantly decreased only in patients aged 55 years and older who had undergone 3 or 4 treatment cycles. In men, CBC was more affected by cumulative dose. ¹³¹I therapy only influenced platelet and monocyte counts in patients aged 55 years or older. Hb was significantly decreased and increased in the high- and low-dose groups, respectively. No significant complications were observed during follow-up. CONCLUSIONS ¹³¹I therapy had a greater impact on WBC counts in women, while changes in RBC counts and Hb were more obvious in men. During ¹³¹I therapy, clinicians should pay attention to different CBC indicators based on a patient's sex and age, but risks associated with an altered CBC are unlikely to outweigh the benefits of 131I. The results of the present study may help alleviate the concerns of a large proportion of patients with DTC and their families about the effects of ¹³¹I therapy on CBC.

An unusual case of reactivated latent pulmonary cryptococcal infection in a patient after short-term steroid and azathioprine therapy: a case report.

BACKGROUND: Cryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before. CASE PRESENTATION: A 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient's history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed. CONCLUSIONS: Although rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.

Nonreciprocal Goos-Hänchen shift by topological edge states of a magnetic photonic crystal.

We demonstrate that a topological edge state can enhance the Goos-Hänchen (GH) shift on the interface of a magnetic photonic crystal (MPC) fabricated by ferrite rings in a square lattice. The GH shift is nonreciprocal because of the time reversal symmetry breaking, and the shift is negative, which is associated with the incident angles and direction of bias DC magnetic field. In particular, the nonreciprocal GH shift presents at normal incidence, and is further verified by experiments. The nonreciprocal negative GH shifts provide a new way to control the flow of light, which could be applied to sensing and even the slow light waveguide to trap the light.

Compact patch antenna enabled by a metasurface with stereo elements.

We implemented a novel compact antenna by applying a metasurface with stereo elements (stereo-MS) as the superstrate of a patch antenna. The stereo-MS, an array of stereo patches printed on a grooved dielectric substrate, enabled the footprint miniaturization and bandwidth enhancement of the patch antenna. The overall size reduction of the stereo-MS antenna is over 38% compared with the conventional plane metasurface (plane-MS) antenna working in the same frequency range. A prototype antenna working at 5.3 GHz was designed, fabricated, and measured. Experiments demonstrated the fractional impedance bandwidth of the antenna was 44.5% at criteria |S11 |< -10 dB, covering the frequencies 4.18 to 6.56 GHz, and the average gain about 6.9 dBi in the band. Experimental results were found in very good agreement with the design, which confirms the functionality of stereo-MS in antenna minimization. Our antenna features a compact size (0.409 λ02) and low profile (3.024 mm). The stereo-MSs provide a new way for the size miniaturization of microwave and optical devices, such as antennas.

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways.

Although macrophage (Mφ) polarization has been demonstrated to play crucial roles in cellular osteogenesis across the cascade of events in periodontal regeneration, how polarized Mφ phenotypes influence the cementoblastic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. In the present study, human monocyte leukemic cells (THP-1) were induced into M0, M1, and M2 subsets, and the influences of these polarized Mφs on the cementoblastic differentiation of PDLSCs were assessed in both conditioned medium-based and Transwell-based coculture systems. Furthermore, the potential pathways and cyto-/chemokines involved in Mφ-mediated cementoblastic differentiation were screened and identified. In both systems, M2 subsets increased cementoblastic differentiation-related gene/protein expression levels in cocultured PDLSCs, induced more PDLSCs to differentiate into polygonal and square cells, and enhanced alkaline phosphatase activity in PDLSCs. Furthermore, Akt and c-Jun N-terminal Kinase (JNK) signaling was identified as a potential pathway involved in M2 Mφ-enhanced PDLSC cementoblastic differentiation, and cyto-/chemokines (interleukin (IL)-10 and vascular endothelial growth factor [VEGF]) secreted by M2 Mφs were found to be key players that promoted cell cementoblastic differentiation by activating Akt signaling. Our data indicate for the first time that Mφs are key modulators during PDLSC cementoblastic differentiation and are hence very important for the regeneration of multiple periodontal tissues, including the cementum. Although the Akt and JNK pathways are involved in M2 Mφ-enhanced cementoblastic differentiation, only the Akt pathway can be activated via a cyto-/chemokine-associated mechanism, suggesting that players other than cyto-/chemokines also participate in the M2-mediated cementoblastic differentiation of PDLSCs. Stem Cells 2019;37:1567-1580.

Near-Field Communication Sensors.

Near-field communication is a new kind of low-cost wireless communication technology developed in recent years, which brings great convenience to daily life activities such as medical care, food quality detection, and commerce. The integration of near-field communication devices and sensors exhibits great potential for these real-world applications by endowing sensors with new features of powerless and wireless signal transferring and conferring near field communication device with sensing function. In this review, we summarize recent progress in near field communication sensors, including the development of materials and device design and their applications in wearable personal healthcare devices. The opportunities and challenges in near-field communication sensors are discussed in the end.

The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells.

Macrophages (Mφs) are involved in a variety of physiological and pathological events including wound healing and tissue regeneration, in which they play both positive and negative roles depending on their polarization state. In this study, we investigated the cellular behaviours of bone marrow mesenchymal stem cells (BMMSCs) after incubation in different conditioned media (CMs) generated by unpolarized Mφs (M0) or polarized Mφs (M1 and M2). Mφ polarization was induced by stimulation with various cytokines, and CMs were obtained from in vitro Mφ cultures termed CM0, CM1 and CM2 based on each Mφ phenotype. We found that CM1 supported the proliferation and adipogenic differentiation of BMMSCs, whereas CM0 had a remarkable effect on cell osteogenic differentiation. To a certain degree, CM2 also facilitated BMMSC osteogenesis; in particular, cells incubated with CM2 exhibited an enhanced capacity to form robust stem cell sheets. Although incubation with CM1 also increased production of extracellular matrix components, such as fibronectin, COL-1 and integrin ß1during sheet induction, the sheets generated by CM2-incubated cells were thicker than those generated by CM1-incubated cells (P < 0.001). Our data suggest that each Mφ phenotype has a unique effect on BMMSCs. Fine-tuning Mφ polarization following transplantation may serve as an effective method to modulate the therapeutic potential of BMMSCs.

Transmission and radar cross-section reduction by combining binary coding metasurface and frequency selective surface.

A modified reflective metasurface, which is constructed by replacing the metal ground of the reflective coding metasurface with a bandpass frequency-selective surface, is proposed. The metasurface has transmission and reduction of radar cross-section characteristics. This allows the metasurface to overcome the drawbacks of conventional realizations, which use lossy materials. The modified metasurface provides high-efficiency transmission in the passband of a frequency-selective surface and broadband reduction of the radar cross section in the rejection band of the frequency-selective surface. Transmission of -0.24 dB was achieved at 4.6 GHz, as well as a -15 dB reduction of radar cross section from 8.5 to 13.5 GHz. This work provides advancements in metasurface applications.

Broadband backscattering reduction realized by array of lossy scatterers.

We propose an array of randomly distributed lossy scatterers to achieve broadband backscattering reduction. The array efficiently combines absorption and diffusion functionalities by using three subarrays made of ferromagnetic or dielectric scatterers based on resistive octagonal rings. The subarrays have strong absorption in different frequency bands, whereas they have different reflection phases in a wide frequency band, resulting in -10 dB backscattering reduction in a wide frequency range (from 3.15 to 18 GHz). The results are verified by experiments. Our work provides a new way to reduce backscattering in a wider frequency range and at lower frequencies.

Administration of signalling molecules dictates stem cell homing for in situ regeneration.

Ex vivo-expanded stem cells have long been a cornerstone of biotherapeutics and have attracted increasing attention for treating intractable diseases and improving tissue regeneration. However, using exogenous cellular materials to develop restorative treatments for large numbers of patients has become a major concern for both economic and safety reasons. Advances in cell biological research over the past two decades have expanded the potential for using endogenous stem cells during wound healing processes, and in particular, recent insight into stem cell movement and homing has prompted regenerative research and therapy based on recruiting endogenous cells. Inspired by the natural healing process, artificial administration of specific chemokines as signals systemically or at the injury site, typically using biomaterials as vehicles, is a state-of-the-art strategy that potentiates stem cell homing and recreates an anti-inflammatory and immunomodulatory microenvironment to enhance in situ tissue regeneration. However, pharmacologically coaxing endogenous stem cells to act as therapeutics in the field of biomedicine remains in the early stages; its efficacy is limited by the lack of innovative methodologies for chemokine presentation and release. This review describes how to direct the homing of endogenous stem cells via the administration of specific signals, with a particular emphasis on targeted signalling molecules that regulate this homing process, to enhance in situ tissue regeneration. We also provide an outlook on and critical considerations for future investigations to enhance stem cell recruitment and harness the reparative potential of these recruited cells as a clinically relevant cell therapy.

Manipulating electromagnetic wave propagating non-reciprocally by a chain of ferrite rods.

We demonstrated that non-reciprocal wave propagation could be manipulated by a magnetic rod chain under bias DC magnetic fields. Made of ferrite material YIG and designed working in the microwave X-band, the rod chain exhibited almost a total reflection when the incident wave obliquely impinged on the rod chain, but exhibited nearly a total transmission when the wave reversed its propagation direction. The non-reciprocal wave propagation was due to the non-reciprocal diffraction of the rod chain for the orders 0 and ± 1. Further, the non-reciprocal wave propagation was directly observed by using the field mapping technique. The unique non-reciprocal wave property of the magnetic rod chain provides a new way to control the flow of EM waves.