Novel biallelic SASS6 variants associated with primary microcephaly and fetal growth restriction.

Primary microcephaly is characterized by a head circumference prenatally or at birth that falls below three standard deviations from age-, ethnic-, and sex-specific norms. Genetic defects are one of the underlying causes of primary microcephaly. Since 2014, five variants of the SASS6 gene have been identified as the cause of MCPH 14 in three reported families. In this study, we present the genetic findings of members of a nonconsanguineous Chinese couple with a history of microcephaly and fetal growth restriction (FGR) during their first pregnancy. Utilizing trio whole-exome sequencing, we identified compound heterozygous variants involving a frameshift NM_194292.3:c.450_453del p.(Lys150AsnfsTer7) variant and a splice region NM_194292.3:c.1674+3A>G variant within the SASS6 gene in the affected fetus. Moreover, reverse transcriptase-polymerase chain reaction from RNA of the mother's peripheral blood leukocytes revealed that the c.1674+3A>G variant led to the skipping of exon 14 and an inframe deletion. To the best of our knowledge, the association between FGR and SASS6-related microcephaly has not been reported, and our findings confirm the pivotal role of SASS6 in microcephaly pathogenesis and reveal an expanded view of the phenotype and mutation spectrum associated with this gene.

Far-field midinfrared superresolution imaging and spectroscopy of single high aspect ratio gold nanowires.

Limited approaches exist for imaging and recording spectra of individual nanostructures in the midinfrared region. Here we use infrared photothermal heterodyne imaging (IR-PHI) to interrogate single, high aspect ratio Au nanowires (NWs). Spectra recorded between 2,800 and 4,000 cm-1 for 2.5-3.9-µm-long NWs reveal a series of resonances due to the Fabry-Pérot modes of the NWs. Crucially, IR-PHI images show structure that reflects the spatial distribution of the NW absorption, and allow the resonances to be assigned to the m = 3 and m = 4 Fabry-Pérot modes. This far-field optical measurement has been used to image the mode structure of plasmon resonances in metal nanostructures, and is made possible by the superresolution capabilities of IR-PHI. The linewidths in the NW spectra range from 35 to 75 meV and, in several cases, are significantly below the limiting values predicted by the bulk Au Drude damping parameter. These linewidths imply long dephasing times, and are attributed to reduction in both radiation damping and resistive heating effects in the NWs. Compared to previous imaging studies of NW Fabry-Pérot modes using electron microscopy or near-field optical scanning techniques, IR-PHI experiments are performed under ambient conditions, enabling detailed studies of how the environment affects mid-IR plasmons.

Chiral Plasmonic Nanostructures Enabled by Bottom-Up Approaches.

We present a comprehensive review of recent developments in the field of chiral plasmonics. Significant advances have been made recently in understanding the working principles of chiral plasmonic structures. With advances in micro- and nanofabrication techniques, a variety of chiral plasmonic nanostructures have been experimentally realized; these tailored chiroptical properties vastly outperform those of their molecular counterparts. We focus on chiral plasmonic nanostructures created using bottom-up approaches, which not only allow for rational design and fabrication but most intriguingly in many cases also enable dynamic manipulation and tuning of chiroptical responses. We first discuss plasmon-induced chirality, resulting from the interaction of chiral molecules with plasmonic excitations. Subsequently, we discuss intrinsically chiral colloids, which give rise to optical chirality owing to their chiral shapes. Finally, we discuss plasmonic chirality, achieved by arranging achiral plasmonic particles into handed configurations on static or active templates. Chiral plasmonic nanostructures are very promising candidates for real-life applications owing to their significantly larger optical chirality than natural molecules. In addition, chiral plasmonic nanostructures offer engineerable and dynamic chiroptical responses, which are formidable to achieve in molecular systems. We thus anticipate that the field of chiral plasmonics will attract further widespread attention in applications ranging from enantioselective analysis to chiral sensing, structural determination, and in situ ultrasensitive detection of multiple disease biomarkers, as well as optical monitoring of transmembrane transport and intracellular metabolism.

Photothermal Circular Dichroism Induced by Plasmon Resonances in Chiral Metamaterial Absorbers and Bolometers.

Chiral photochemistry remains a challenge because of the very small asymmetry in the chiro-optical absorption of molecular species. However, we think that the rapidly developing fields of plasmonic chirality and plasmon-induced circular dichroism demonstrate very strong chiro-optical effects and have the potential to facilitate the development of chiral photochemistry and other related applications such as chiral separation and sensing. In this study, we propose a new type of chiral spectroscopy-photothermal circular dichroism. It is already known that the planar plasmonic superabsorbers can be designed to exhibit giant circular dichroism signals in the reflection. Therefore, upon illumination with chiral light, such planar metastructures should be able to generate a prominent asymmetry in their local temperatures. Indeed, we demonstrate this chiral photothermal effect using a chiral plasmonic absorber. Calculated temperature maps show very strong photothermal circular dichroism. One of the structures computed in this Letter could serve as a chiral bolometer sensitive to circularly polarized light. Overall, this chiro-optical effect in plasmonic metamaterials is much greater than the equivalent effect in any chiral molecular system or plasmonic bioassembly. Potential applications of this effect are in polarization-sensitive surface photochemistry and chiral bolometers.

Plasmonic Glasses and Films Based on Alternative Inexpensive Materials for Blocking Infrared Radiation.

The need for energy-saving materials is pressing. This Letter reports on the design of energy-saving glasses and films based on plasmonic nanocrystals that efficiently block infrared radiation. Designing such plasmonic composite glasses is nontrivial and requires taking full advantage of both material and geometrical properties of the nanoparticles. We compute the performance of solar plasmonic glasses incorporating a transparent matrix and specially shaped nanocrystals. This performance depends on the shape and material of such nanocrystals. Glasses designed with plasmonic nanoshells are shown to exhibit overall better performances as compared to nanorods and nanocups. Simultaneously, scalable synthesis of plasmonic nanoshells and nanocups is technologically feasible using gas-phase fabrication methods. The computational simulations were performed for noble metals (gold and silver) as well as for alternative plasmonic materials (aluminum, copper, and titanium nitride). Inexpensive plasmonic materials (silver, copper, aluminum, and titanium nitride) show an overall good performance in terms of the commonly used figures of merit of industrial glass windows. Together with numerical data for specific materials, this study includes a set of general rules for designing efficient plasmonic IR-blocking media. The plasmonic glasses proposed herein are good candidates for the creation of cheap optical media, to be used in energy-saving windows in warm climates' housing or temperature-sensitive infrastructure.

Mid-infrared Plasmonic Circular Dichroism Generated by Graphene Nanodisk Assemblies.

It is very interesting to bring plasmonic circular dichroism spectroscopy to the mid-infrared spectral interval, and there are two reasons for this. This spectral interval is very important for thermal bioimaging, and simultaneously, this spectral range includes vibrational lines of many chiral biomolecules. Here we demonstrate that graphene plasmons indeed offer such opportunity. In particular, we show that chiral graphene assemblies consisting of a few graphene nanodisks can generate strong circular dichroism (CD) in the mid-infrared interval. The CD signal is generated due to the plasmon-plasmon coupling between adjacent nanodisks in the specially designed chiral graphene assemblies. Because of the large dimension mismatch between the thickness of a graphene layer and the incoming light's wavelength, three-dimensional configurations with a total height of a few hundred nanometers are necessary to obtain a strong CD signal in the mid-infrared range. The mid-infrared CD strength is mainly governed by the total dimensions (total height and helix scaffold radius) of the graphene nanodisk assembly and by the plasmon-plasmon interaction strength between its constitutive nanodisks. Both positive and negative CD bands can be observed in the graphene assembly array. The frequency interval of the plasmonic CD spectra overlaps with the vibrational modes of some important biomolecules, such as DNA and many different peptides, giving rise to the possibility of enhancing the vibrational optical activity of these molecular species by attaching them to the graphene assemblies. Simultaneously the spectral range of chiral mid-infrared plasmons in our structures appears near the typical wavelength of the human-body thermal radiation, and therefore, our chiral metastructures can be potentially utilized as optical components in thermal imaging devices.

Substrate phonon-mediated plasmon hybridization in coplanar graphene nanostructures for broadband plasmonic circuits.

The mode hybridization between adjacent graphene nanoribbons determines the integration density of graphene-based plasmonic devices. Here, plasmon hybridization in graphene nanostructures is demonstrated through the characterization of the coupling strength of plasmons in graphene nanoribbons as a function of charge density and inter-ribbon spacing using Fourier transform infrared microscopy. In combination with numerical simulations, it is shown that the plasmon coupling is strongly mediated by the substrate phonons. For polar substrates, the plasmon coupling strength is limited by the plasmon-phonon interactions. In contrast, a nonpolar substrate affects neither the energy distribution of the original plasmon modes in graphene nanostructures nor their plasmon interactions, which increases exponentially as the inter-ribbon spacing decreases. To further explore the potential of graphene broadband plasmonics on nonpolar substrates, a scheme is proposed that uses a metal-dielectric heterostructure to prevent the overlap of plasmons between neighboring graphene nanoribbons. The device structures retain the plasmon resonance frequency of the graphene ribbons and maximally isolate the plasmonic components from the surrounding electromagnetic environment, allowing modular design in integrated plasmonic circuits.

Making transient optical reflection of graphene polarization dependent.

The polarization dependence of transient optical reflection, induced by nonequilibrium carriers isotropically distributed in momentum space, of graphene on substrate is experimentally and theoretically investigated. It is found that this transient optical reflection could be made greatly polarization dependent by using oblique incidence for light, and the characteristic of this polarization dependence could be flexibly altered with incident angle and incident direction (from graphene to substrate, or from substrate to graphene). Our results suggest that through polarization of incident beam is an efficient way of manipulating graphene transient optical reflection.

Graphene plasmon propagation on corrugated silicon substrates.

The scheme of graphene on a silicon substrate is potentially compatible to the microelectronic technology. But the maintained plasmons have considerable ohmic loss because of silicon's large permittivity. We introduce air grooves in the silicon surface to reduce the optical thickness of substrate and hence decrease the propagation loss. The properties of graphene plasmons on the corrugated substrates are numerically investigated, in terms of the photon frequency and the geometrical parameters of the corrugated layer, considering both ohmic loss and scattering loss. The plasmons propagation lengths for the corrugated substrates can exceed twice of those for flat silicon in a broadband in mid-infrared. This study may be useful for designing of compact mid-infrared waveguides based on graphene for future photonic integrated circuits.

Plasmonic extinction of gated graphene nanoribbon array analyzed by a scaled uniform Fermi level.

A uniform Fermi level profile is typically assumed in the analysis of a gated graphene nanoribbon, whose Fermi level is actually nonuniform in the experimental measurements. Here, we show that the uniform Fermi level has to be downshifted when it is used to analyze a backgated graphene nanoribbon array (GNRA). The plasmonic extinction behaviors of the GNRAs are perfectly preserved by assuming properly scaled uniform Fermi levels. The scaling factor is independent of the average value of the actual Fermi level profile, but it is a function of the ratio of the nanoribbon width to the distance of the nanoribbons from the backgate. This study facilitates the data postprocessing in the experiments, and may be helpful for analyzing the electron behaviors in GNRAs.

Regulation of androgen receptor activity by tyrosine phosphorylation.

The androgen receptor (AR) is essential for the growth of prostate cancer cells. Here, we report that tyrosine phosphorylation of AR is induced by growth factors and elevated in hormone-refractory prostate tumors. Mutation of the major tyrosine phosphorylation site in AR significantly inhibits the growth of prostate cancer cells under androgen-depleted conditions. The Src tyrosine kinase appears to be responsible for phosphorylating AR, and there is a positive correlation of AR tyrosine phosphorylation with Src tyrosine kinase activity in human prostate tumors. Our data collectively suggest that growth factors and their downstream tyrosine kinases, which are elevated during hormone-ablation therapy, can induce tyrosine phosphorylation of AR and such modification may be important for prostate tumor growth under androgen-depleted conditions.

Prenatal diagnosis and preimplantation genetics testing of 3M syndrome in a Chinese family with novel biallelic variants of CUL7.

BACKGROUND: 3M syndrome is a rare autosomal recessive developmental disorder characterized by pre and postnatal growth deficiency, dysmorphic facial features, and normal intelligence. 3M syndrome should be suspected in a proband with a combination of characteristic or recognizable dysmorphic features. The diagnosis of 3M syndrome could be confirmed by identifying biallelic variants in CUL7, OBSL1, or CCDC8. METHODS: Whole-exome sequencing (WES) was performed to identify genetic causes. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to detect aberrant splicing events. Haplotypes were constructed using multiplex PCR and sequencing. Variants of the parental haplotype and target likely pathogenic variants were detected by PCR and Sanger sequencing from the embryos. Copy number variant (CNV) detection was performed by next-generation sequencing. RESULTS: We present the case of a nonconsanguineous Chinese couple with one abnormal pregnancy, where the fetus showed 3M phenotypes of shortened long bones. WES identified two novel heterozygous mutations in CUL7: NM_014780.5:c.354del (p.Gln119ArgfsTer52) and NM_014780.5:c.1373-15G>A. RT-PCR from RNA of the mother's peripheral blood leucocytes showed that c.1373-15G>A caused the insertion of a 13-bp extra intron sequence and encoded the mutant p.Leu459ProfsTer25. Both variants were classified as likely pathogenic according to ACMG/AMP guidelines and Clinical Genome Resource specifications. During genetic counseling, the options of prenatal diagnosis through chorionic villus sampling or amniocentesis, adoption, sperm donation, and electing not to reproduce, as well as preimplantation genetic testing for monogenic disorders (PGT-M), were discussed. The couple hopes to conceive a child of their own and refused to accept the 25% risk during the next pregnancy and opted for PGT-M. They finally successfully delivered a healthy baby through PGT-M. CONCLUSION: This study expanded the mutation spectrum of CUL7, detected the aberrant splicing event of CUL7 via RT-PCR, constructed the haplotype for PGT-M, and demonstrated the successful delivery of a healthy baby using PGT-M.

Clinical value of screening prenatal ultrasound combined with chromosomal microarrays in prenatal diagnosis of chromosomal abnormalities.

OBJECTIVE: To evaluate the clinical value of ultrasound findings in the screening of fetal chromosomal abnormalities and the analysis of risk factors for chromosome microarray analysis (CMA) abnormalities. METHODS: We retrospectively analyzed the datasets of 15,899 pregnant women who underwent prenatal evaluations at Affiliated Maternity and Child Health Care Hospital of Nantong University between August 2018 and December 2022. Everyone underwent ultrasound screening, and those with abnormal findings underwent CMA to identify chromosomal abnormalities. RESULTS: The detection rates for isolated ultrasound anomalies and combined ultrasound and CMA anomalies were 11.81% (1877/15,899) and 2.40% (381/15,899), respectively. Among all ultrasound abnormalities, detection rates for isolated ultrasound soft marker anomalies, isolated structural abnormalities, and both ultrasound soft marker anomalies with structural abnormalities were 82.91% (1872/2258), 15.99% (361/2258), and 1.11% (25/2258), respectively. The detection rate of abnormal chromosomes in pregnant women with abnormal ultrasound results was 16.87% (381/2258). The detection rates were 13.33% in cases with two or more ultrasound soft markers anomalies, 47.37% for two or more structural anomalies, and 48.00% for concomitant ultrasound soft marker and structural anomalies. CONCLUSIONS: Enhanced detection rates of chromosomal anomalies in fetal malformations are achieved with specific ultrasound findings (NT thickening, cardiovascular abnormalities, and multiple soft markers) or when combined with high-risk factors (advanced maternal age, familial history, parental chromosomal anomalies, etc.). When the maternal age is over 35 and with ≥2 ultrasound soft marker anomalies accompanied with any high-risk factors, CMA testing can aid in the diagnosis of prenatal chromosomal abnormalities.

Mode converter in metal-insulator-metal plasmonic waveguide designed by transformation optics.

A metal-insulator-metal (MIM) waveguide can support two plasmonic modes. Efficient conversion between the two modes can be achieved by reshaping of both phase and power density distributions of the guided mode. The converters are designed with the assistance of transformation optics. We propose two practical configurations for mode conversion, which only consist of homogeneous materials yielded from linear coordinate transformations. The functionalities of the converters are demonstrated by full wave simulations. Without consideration of transmission loss, conversion efficiency of as high as 95% can be realized.

Nanostructure fabricated by nanosphere lithography assisted with O2 plasma treatment.

Nanosphere lithography is an efficient way to fabricate metallic nanostructures with large area. This paper presents the fabrication of metallic hexagonal nano-pyramid arrays by two dimensional nanospheres lithography assisted with O2 plasma treatment. By O2 plasma treatment, the gap and diameter of nanospheres can be modulated. After electron beam deposition, we can fabricate similar nanostructures with different pyramid gap distances. This method may be an easy way to modulate the geometric parameters of nanostructures.

Dealing With Missing, Imbalanced, and Sparse Features During the Development of a Prediction Model for Sudden Death Using Emergency Medicine Data: Machine Learning Approach.

BACKGROUND: In emergency departments (EDs), early diagnosis and timely rescue, which are supported by prediction modes using ED data, can increase patients' chances of survival. Unfortunately, ED data usually contain missing, imbalanced, and sparse features, which makes it challenging to build early identification models for diseases. OBJECTIVE: This study aims to propose a systematic approach to deal with the problems of missing, imbalanced, and sparse features for developing sudden-death prediction models using emergency medicine (or ED) data. METHODS: We proposed a 3-step approach to deal with data quality issues: a random forest (RF) for missing values, k-means for imbalanced data, and principal component analysis (PCA) for sparse features. For continuous and discrete variables, the decision coefficient R2 and the κ coefficient were used to evaluate performance, respectively. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were used to estimate the model's performance. To further evaluate the proposed approach, we carried out a case study using an ED data set obtained from the Hainan Hospital of Chinese PLA General Hospital. A logistic regression (LR) prediction model for patient condition worsening was built. RESULTS: A total of 1085 patients with rescue records and 17,959 patients without rescue records were selected and significantly imbalanced. We extracted 275, 402, and 891 variables from laboratory tests, medications, and diagnosis, respectively. After data preprocessing, the median R2 of the RF continuous variable interpolation was 0.623 (IQR 0.647), and the median of the κ coefficient for discrete variable interpolation was 0.444 (IQR 0.285). The LR model constructed using the initial diagnostic data showed poor performance and variable separation, which was reflected in the abnormally high odds ratio (OR) values of the 2 variables of cardiac arrest and respiratory arrest (201568034532 and 1211118945, respectively) and an abnormal 95% CI. Using processed data, the recall of the model reached 0.746, the F1-score was 0.73, and the AUROC was 0.708. CONCLUSIONS: The proposed systematic approach is valid for building a prediction model for emergency patients.

Optical properties of metal-multi-insulator-metal plasmonic waveguides.

We theoretically study the plasmonic modes in metal-multi-insulator-metal (MMIM) waveguides. Two types of symmetric MMIM structures consisting of three insulators are investigated thoroughly. The effective refractive index, energy confinement, propagation length, and figure of merit are given in terms of geometric parameters. Due to the step index modulation, these properties of MMIM structures differ from the metal-insulator-metal (MIM) structure. Compared with the corresponding MIM structures, MMIM structures can possess either better energy confinement or larger propagation length, which depends on the geometric parameters and the index distribution. Propagation length of up to 10(3) µm and a figure of merit of up to 10(4) are observed for MMIM structure with core thickness of several hundred nanometers.

Case Report: Novel Biallelic Null Variants of SMPD4 Confirm Its Involvement in Neurodevelopmental Disorder With Microcephaly, Arthrogryposis, and Structural Brain Anomalies.

The SMPD4 gene encodes sphingomyelin phosphodiesterase 4, which preferentially hydrolyzes sphingomyelin over other phospholipids. The biallelic loss-of-function variants of SMPD4 have been identified in a group of children with neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA). Here, we report a girl of Chinese ancestry with intrauterine growth restriction, microcephaly, postnatal developmental delay, arthrogryposis, hypertonicity, seizure, and hypomyelination on brain magnetic resonance imaging; biallelic null variants (c.1347C > G [p.Tyr449*]; Chr2 [GRCh37]: g.130877574_131221737del [whole-gene deletion]) were detected by whole-exome sequencing. Our case is the first report of NEDMABA of Chinese ancestry, confirming the involvement of SMPD4 in NEDMABA and expanding the mutation spectrum of this syndrome.

Social Support and Family Functioning during Adolescence: A Two-Wave Cross-Lagged Study.

The influence of social and family factors on adolescent mental health has been widely valued. Considering adolescents' family systems in a broader social context facilitates a better understanding of their mental health, which also has special significance in the post-epidemic era. The purpose of the present study was to explore the relationship between social support and family functioning during adolescence. Students from two middle schools in Fujian province, China, were recruited as participants. Seven hundred and fifty-four participants completed the questionnaire twice in six-month intervals. We constructed a cross-lagged model by using IBM SPSS AMOS 26.0 to test the relationship between these two variables. Social support and family functioning predicted each other in the girls, but not for the boys' sample. The results of this study suggested that the interaction between family and social factors and the possible gender differences should be considered when dealing with adolescents' mental health problems.

Synergistic Combination of Charge Carriers and Energy-Transfer Processes in Plasmonic Photocatalysis.

Important efforts are currently under way in order to develop further the nascent field of plasmonic photocatalysis, striving for improved efficiencies and selectivities. A significant fraction of such efforts has been focused on distinguishing, understanding, and enhancing specific energy-transfer mechanisms from plasmonic nanostructures to their environment. Herein, we report a synthetic strategy that combines two of the main physical mechanisms driving plasmonic photocatalysis into an engineered system by rationally combining the photochemical features of energetic charge carriers and the electromagnetic field enhancement inherent to the plasmonic excitation. We do so by creating hybrid photocatalysts that integrate multiple plasmonic resonators in a single entity, controlling their joint contribution through spectral separation and differential surface functionalization. This strategy allows us to create complex hybrids with improved photosensitization capabilities, thanks to the synergistic combination of two photosensitization mechanisms. Our results show that the hot electron injection can be combined with an energy-transfer process mediated by the near-field interaction, leading to a significant increase in the final photocatalytic response of the material and moving the field of plasmonic photocatalysis closer to energy-efficient applications. Furthermore, our multimodal hybrids offer a test system to probe the properties of the two targeted mechanisms in energy-related applications such as the photocatalytic generation of hydrogen and open the door to wavelength-selective photocatalysis and novel tandem reactions.