Integrating Sulfur Doping with a Multi-Heterointerface Fe7S8/NiS@C Composite for Wideband Microwave Absorption.

Heterointerface engineering is presently considered a valuable strategy for enhancing the microwave absorption (MA) properties of materials via compositional modification and structural design. In this study, a sulfur-doped multi-interfacial composite (Fe7S8/NiS@C) coated with NiFe-layered double hydroxides (LDHs) is successfully prepared using a hydrothermal method and post-high-temperature vulcanization. When assembled into twisted surfaces, the NiFe-LDH nanosheets exhibit porous morphologies, improving impedance matching, and microwave scattering. Sulfur doping in composites generates heterointerfaces, numerous sulfur vacancies, and lattice defects, which facilitate the polarization process to enhance MA. Owing to the controllable heterointerface design, the unique porous structure induced multiple heterointerfaces, numerous vacancies, and defects, endowing the Fe7S8/NiS@C composite with an enhanced MA capability. In particular, the minimum reflection loss (RLmin) value reached -58.1 dB at 15.8 GHz at a thickness of 2.1 mm, and a broad effective absorption bandwidth (EAB) value of 7.3 GHz is achieved at 2.5 mm. Therefore, the Fe7S8/NiS@C composite exhibits remarkable potential as a high-efficiency MA material owing to the synergistic effects of the polarization processes, multiple scatterings, porous structures, and impedance matching.

Spectral Engineering of Optical Microresonators in Anisotropic Lithium Niobate Crystal.

On-chip optical microresonators are essential building blocks in integrated optics. The ability to arbitrarily engineer their resonant frequencies is crucial for exploring novel physics in synthetic frequency dimensions and practical applications like nonlinear optical parametric processes and dispersion-engineered frequency comb generation. Photonic crystal ring (PhCR) resonators are a versatile tool for such arbitrary frequency engineering, by controllably creating mode splitting at selected resonances. To date, these PhCRs have mostly been demonstrated in isotropic photonic materials, while such engineering can be significantly more complicated in anisotropic platforms that often offer more fruitful optical properties. Here, the spectral engineering of chip-scale optical microresonators is realized in the anisotropic lithium niobate (LN) crystal by a gradient design that precisely compensates for variations in both refractive index and perturbation strength. Controllable frequency splitting is experimentally demonstrated at single and multiple selected resonances in LN PhCR resonators with different sizes, while maintaining high quality-factors up to 1 × 106. Moreover, a sharp boundary is experimentally constructed in the synthetic frequency dimension based on an actively modulated x-cut LN gradient-PhCR, opening up new paths toward the arbitrary control of electro-optic comb spectral shapes and exploration of novel physics in the frequency degree of freedom.

Porous polydimethylsiloxane films with specific surface wettability but distinct regular physical structures fabricated by 3D printing.

Porous polydimethylsiloxane (PDMS) films with special surface wettability have potential applications in the biomedical, environmental, and structural mechanical fields. However, preparing porous PDMS films with a regular surface pattern using conventional methods, such as chemical foaming or physical pore formation, is challenging. In this study, porous PDMS films with a regular surface pattern are designed and prepared using 3D printing to ensure the formation of controllable and regular physical structures. First, the effect of the surface wettability of glass substrates with different surface energies (commercial hydrophilic glass and hydrophobic glass (F-glass) obtained by treating regular glass with 1H,1H,2H,2H-perfluorooctyl-trichlorosilane) on the structural characteristics of the 3D printed PDMS filaments is investigated systematically. Additionally, the effect of the printing speed and the surface wettability of the glass substrate on the PDMS filament morphology is investigated synchronously. Next, using the F-glass substrate and an optimized printing speed, the effects of the number of printed layers on both the morphologies of the individual PDMS filaments and porous PDMS films, and the surface wettability of the films are studied. This study reveals that regularly patterned porous PDMS films with distinct structural designs but the same controllable surface wettability, such as anisotropic surface wettability and superhydrophobicity, can be easily fabricated through 3D printing. This study provides a new method for fabricating porous PDMS films with a specific surface wettability, which can potentially expand the application of porous PDMS films.

Design and resonator-assisted characterization of high-performance lithium niobate waveguide crossings.

Waveguide crossings are elementary passive components for signal routing in photonic integrated circuits. Here, we design and characterize two multimode interferometer (MMI)-based waveguide crossings to serve the various routing directions in the anisotropic x-cut thin-film lithium niobate (TFLN) platform. To address the large measurement uncertainties in traditional cut-back characterization methods, we propose and demonstrate a resonator-assisted approach that dramatically reduces the uncertainty of insertion loss measurement (< 0.021 dB) and the lower bound of crosstalk measurement (-60 dB) using only two devices. Based on this approach, we demonstrate and verify TFLN waveguide crossings with insertion losses of < 0.070 dB and crosstalk of < -50 dB along all three routing directions at 1550 nm. The low-loss and low-crosstalk waveguide crossings in this work, together with the simple and efficient characterization strategy, could provide important layout design flexibility for future large-scale classical and quantum TFLN photonic circuits.

Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

Comparison of acute respiratory distress syndrome in patients with COVID-19 and influenza A (H7N9) virus infection.

OBJECTIVES: We aimed to compared the clinical features of acute respiratory distress syndrome (ARDS) induced by COVID-19 and H7N9 virus infections. METHODS: Clinical data of 100 patients with COVID-19 and 46 patients with H7N9 were retrospectively analyzed. RESULTS: Elevated inflammatory indices and coagulation disorders were more common in COVID-19-ARDS group than in the H7N9-ARDS group. The median interval from illness onset to ARDS development was shorter in H7N9-ARDS. The PaO2/FiO2 level was lower in H7N9-ARDS, whereas the Sepsis-related Organ Failure Assessment score was higher in COVID-19-ARDS. The proportion of patients with disseminated intravascular coagulation and liver injury in COVID-19-ARDS and H7N9-ARDS was 45.5% versus 3.1% and 28.8% versus 50%, respectively (P <0.05). The mean interval from illness onset to death was shorter in H7N9-ARDS. A total of 59.1% patients with H7N9-ARDS died of refractory hypoxemia compared with 28.9% with COVID-19-ARDS (P = 0.014). Patients with COVID-19-ARDS were more likely to die of septic shock and multiple organ dysfunction compared with H7N9-ARDS (71.2% vs 36.4%, P = 0.005). CONCLUSION: Patients with H7N9 were more susceptible to develop severe ARDS and showed a more acute disease course. COVID-19-ARDS was associated with severe inflammatory response and coagulation dysfunction, whereas liver injury was more common in H7N9-ARDS. The main causes of death between patients with the two diseases were different.

Knockdown of myorg leads to brain calcification in zebrafish.

Primary familial brain calcification (PFBC) is a neurogenetic disorder characterized by bilateral calcified deposits in the brain. We previously identified that MYORG as the first pathogenic gene for autosomal recessive PFBC, and established a Myorg-KO mouse model. However, Myorg-KO mice developed brain calcifications until nine months of age, which limits their utility as a facile PFBC model system. Hence, whether there is another typical animal model for mimicking PFBC phenotypes in an early stage still remained unknown. In this study, we profiled the mRNA expression pattern of myorg in zebrafish, and used a morpholino-mediated blocking strategy to knockdown myorg mRNA at splicing and translation initiation levels. We observed multiple calcifications throughout the brain by calcein staining at 2-4 days post-fertilization in myorg-deficient zebrafish, and rescued the calcification phenotype by replenishing myorg cDNA. Overall, we built a novel model for PFBC via knockdown of myorg by antisense oligonucleotides in zebrafish, which could shorten the observation period and replenish the Myorg-KO mouse model phenotype in mechanistic and therapeutic studies.

GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy.

OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.

Effects of potassium additives on the combustion behavior of chrysanthemum biochar blended with graphite carbon as a heating source for heat-not-burn tobacco.

Heat-not-burn tobacco with an external heating source is a cleaner alternative to conventional cigarettes due to its lower emission of nicotine, CO and tar in the smoke, and the co-combustion of the composite carbon source (chrysanthemum biochar blended with graphite carbon) is a promising carbon heating source for a heat-not-burn tobacco product. This work has investigated the effect of the blending ratio of the graphite carbon on the co-combustion characteristics (i.e., the minimum ignition temperature, the burnout temperature, etc.) of the composite carbon source, as well as the effect of K2CO3 on the co-combustion behaviors. The results indicate that the minimum ignition temperature is mainly controlled by the ignition of the biochar while the burnout temperature is dominated by that of the graphite. The minimum ignition temperature of the carbon mixture is decreased by only 2-17 °C with K2CO3 because the ignition temperature of the biochar is difficult to reduce further by adding K2CO3. Simultaneously, the burnout temperature can be reduced by 30-60 °C since the graphite firing can be significantly improved by the presence of K2CO3. Moreover, the promotion effect of K2CO3 on the co-firing process is not always proportional to the addition amount of the catalyst, especially when the mass fraction of the graphite exceeds the threshold value of 30% based on the observation of the activation energies from the third-order kinetic model analysis.

Synergistic Effect of Sic Particles and Whiskers on the Microstructures and Mechanical Properties of Ti(C,N)-Based Cermets.

The microstructure and mechanical properties of Ti(C,N)-based cermets with the addition of the SiC particles (SiCp) and SiC whiskers (SiCw), were systematically studied in this work. Firstly, the effect of SiCp on the cermets was investigated independently to determine the considerable total amounts of additives, and the results showed that 2.0 wt.% SiCp would lead to optimal properties of the cermet. Then, the influence of SiCp and SiCw additions with the variable ratio on the cermets was studied. The results indicated that when 1.5 wt.% SiCp and 0.5 wt.% SiCw were added; the cermets appeared with the best comprehensive properties, and the transverse rupture strength, hardness, and the fracture toughness of the cermets reached 2520.8 MPa, 88.0 HRA, and 16.56 MPa·m1/2, respectively. This was due to the synergistic strengthening and toughening effect afforded by the reasonable SiCp and SiCw addition, from which the smallest grain size, as well as the most uniform, and completed core-rim structure of the cermets, were achieved.

Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study.

INTRODUCTION: Hereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been reported. HSPs have the same core clinical features, including progressive spasticity in the lower limbs, though HSPs are heterogeneous (eg, clinical signs, MRI features, gene mutation). The age of onset varies greatly, from infant to adulthood. In addition, the slow and variable rates of disease progression in patients with HSP represent a substantial challenge for informative assessment of therapeutic efficacy. To address this, we are undertaking a prospective cohort study to investigate genetic-clinical characteristics, find surrogates for monitoring disease progress and identify clinical readouts for treatment. METHODS AND ANALYSIS: In this case-control cohort study, we will enrol 200 patients with HSP and 200 healthy individuals in parallel. Participants will be continuously assessed for 3 years at 12-month intervals. Six aspects, including clinical signs, genetic spectrum, cognitive competence, MRI features, potential biochemical indicators and nerve electrophysiological factors, will be assessed in detail. This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities. The analysis will also assess disease progression in different types of HSPs and cellular pathways with a longitudinal study using t tests and χ2 tests. ETHICS AND DISSEMINATION: The study was granted ethics committee approval by the first affiliated hospital of Fujian Medical University (MRCTA, ECFAH of FMU (2019)194) in 2019. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public. TRIAL REGISTRATION NUMBER: NCT04006418.

Advances in gene therapy for neurogenetic diseases: a brief review.

Neurogenetic diseases are neurological conditions with a genetic cause (s). There are thousands of neurogenetic diseases, and most of them are incurable. The development of bioinformatics and elucidation of the mechanism of pathogenesis have allowed the development of gene therapy approaches, which show great potential in treating neurogenetic diseases. Viral vectors delivery, antisense oligonucleotides, gene editing, RNA interference, and burgeoning viroid delivery technique are promising gene therapy strategies, and commendable therapeutic effects in the treatment of neurogenetic diseases have been achieved (Fig. 1). This review highlights a sampling of advances in gene therapies for neurogenetic disorders. Fig. 1 Examples of gene therapy strategies used in the treatment of neurogenetic diseases. The schematic diagram shows different gene therapy approaches used for treating a sampling of neurogenetic disorders, such as ASO therapy, gene editing, gene augmentation, and RNA interference.

ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of ß-catenin by upregulating the E3 ligase NEDD4L.

Lung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found thus far. Considering ß, ß-dimethyl-acryl-alkannin (ALCAP2), a natural small-molecule compound isolated from the root of Lithospermum erythrorhizon. We found that lung adenocarcinoma (LUAD) cell proliferation and metastasis can be significantly inhibited after treatment with ALCAP2 in vitro, as it can induce cell apoptosis and arrest the cell cycle. ALCAP2 also significantly suppressed the volume of tumours in mice without inducing obvious toxicity in vivo. Mechanistically, we revealed that ALCAP2-treated cells can suppress the nuclear translocation of ß-catenin by upregulating the E3 ligase NEDD4L, facilitating the binding of ubiquitin to ß-catenin and eventually affecting the wnt-triggered transcription of genes such as survivin, cyclin D1, and MMP9. As a result, our findings suggest that targeting the oncogene ß-catenin with ALCAP2 can inhibit the proliferation and metastasis of LUAD cells, and therefore, ALCAP2 may be a new drug candidate for use in LUAD therapeutics.

Investigation on the micromorphology and thermophysical properties of NaNO3 heat storage materials modified by solution combustion.

Nitrate has a wide temperature range, wide operating temperature, low vapor pressure, low cost, strong heat transfer and stable chemical properties. It is widely used in solar thermal power generation heat storage material. In this paper, the alkali salt NaNO3 was modified by solution combustion method with citric acid as fuel. The structure and thermal properties of the prepared salts were studied by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The results show that the solution combustion process improves the structure and thermal properties of NaNO3, and the resulting product has a new phase. The particle size and microscopic morphology of the prepared salt were changed. As the proportion of fuel increases, the hollow cuboid structure gradually grows on the surface and inside of the modified salt. The microstructure obtained is different at different ignition temperatures, and a finer and even rod-like structure is obtained at an ignition temperature of 600 °C. The specific heat capacity of all modified samples has been improved, among which solid specific heat and liquid specific heat have increased the most, respectively 3.10 J/g·K and 3.19 J/g·K, which are 140.31% and 131.16% higher than the base salt, respectively. This work not only studies the specific heat capacity of NaNO3 modified by solution combustion, but also explores the effect of micromorphology and new phase formation on its performance, which provides innovative ideas for improving the specific heat capacity of molten salt heat storage materials.

Voltage tunable mid-wave infrared reflective varifocal metalens via an optomechanic cavity.

Metalenses enable the multifunctional control of light beams with an optically thin layer of nanoantennas. Efficient on-chip voltage tuning of the focal length is the crucial step toward the integration of metalenses into dynamically tunable optical systems. We propose and numerically investigate the on-chip electrical tuning of a reflective metalens via an optomechanic cavity. Light is focused by an array of silicon nanopillar antennas separated from a deformable metallic reflector by a small air gap. A transparent electrode is inserted into the optomechanic cavity to electrostatically deform the reflector and rearrange the reflection phase profile, resulting in a shift in the focal point. Two modes of voltage tuning via the relative curvature change of the reflector are analyzed. In mode 1, the size of the air gap is modified through the nearly parallel shift of the reflector, whereas in mode 2, the distribution of the air-gap size is tailored by the curvature change of the reflector. With the designed working wavelength of 3.8 µm and the initial focal length of 80.35 µm, the focal length is shifted by 20.3 µm in mode 1 and 7.25 µm in mode 2. Such a device can be used as a free space coupler between quantum cascade lasers and mid-infrared fibers with variable coupling efficiency.

Moesin Is a Novel Biomarker of Endothelial Injury in Sepsis.

OBJECTIVE: Increased vascular permeability and inflammation are principal hallmark of sepsis. Moesin (MSN) is a membrane-associated cytoskeleton protein and crucial for the vascular endothelial function. This study is aimed at evaluating the role of MSN in endothelial injury during the process of sepsis. METHODS: Serum MSN in septic patients was measured by ELISA. BALB/c mice were injected with different doses of lipopolysaccharide (LPS) or underwent cecal ligation and single or double puncture (CLP) to mimic sublethal and lethal sepsis. After treatment, their serum MSN and PCT levels, wet to dry lung weights (W/D ratio), bronchoalveolar lavage fluid (BALF) protein concentrations, and lung injury scores were measured. The impact of MSN silencing on LPS-altered Rock1/myosin light chain (MLC), NF-κB, and inflammatory factors in human microvascular endothelial cells (HMECs), as well as monolayer HMEC permeability, was tested in vitro. RESULTS: Compared with healthy controls, serum MSN increased in septic patients and was positively correlated with SOFA scores and serum PCT levels in septic patients. LPS injection significantly increased serum the MSN and PCT expression, BALF protein levels, and W/D ratio, and the serum MSN levels were positively correlated with serum PCT, lung W/D ratio, and lung injury scores in mice. Similar results were obtained in the way of CLP modelling. LPS enhanced MSN, MLC, NF-κB phosphorylation, increased Rock1 expression, and inflammatory factors release in the cultured HMECs, while MSN silencing significantly mitigated the LPS-induced Rock1 and inflammatory factor expression, NF-κB, and MLC phosphorylation as well as the monolayer hyperpermeability in HMECs. CONCLUSIONS: Increased serum MSN contributes to the sepsis-related endothelium damages by activating the Rock1/MLC and NF-κB signaling and may be a potential biomarker for evaluating the severity of sepsis.

Determining Essential Requirements for Fluorophore Selection in Various Fluorescence Applications Taking Advantage of Diverse Structure-Fluorescence Information of Chromone Derivatives.

Herein, we report our work exploring the essential requirements for fluorophore selection during the development of various fluorescence applications. We assembled a library of chromone-derived fluorophores with diverse structure-fluorescence properties, which allowed us to choose the fluorophore pairs with similar structures but differing fluorescence properties and compared the performance of the selected fluorophore pairs in three types of commonly used fluorescence applications. We found that the selection standard of a suitable fluorophore is variable depending on the application. (1) In fluorescence imaging, fluorophores with strong and constant fluorescence under various conditions, such as a large pH range, are preferred. Notably, (2) in the detection of bioactive species, fluorophores with relatively lower fluorescence quantum yield favor the detection sensitivity. Furthermore, (3) in enzymatic assays employing fluorescence, the key parameter is the binding affinity between the fluorophore and the enzyme.