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.

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.

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.

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.

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.

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.

Chiral Optofluidics with a Plasmonic Metasurface Using the Photothermal Effect.

Plasmonic metasurfaces with the photothermal effect have been increasingly investigated for optofluidics. Meanwhile, along with the expanding application of circularly polarized light, a growing number of investigations on chiral plasmonic metasurfaces have been conducted. However, few studies have explored the chirality and the thermal-induced convection of such systems simultaneously. This paper aims to theoretically investigate the dynamics of the thermally induced fluid convection of a chiral plasmonic metasurface. The proposed metasurface exhibits giant circular dichroism in absorption and thus leads to a strong photothermal effect. On the basis of the multiphysical analysis, including optics, thermodynamics, and hydrodynamics, we propose a concept of chiral spectroscopy termed optofluidic circular dichroism. Our results show that different fluid velocities of thermally induced convection appear around a chiral plasmonic metasurface under different circularly polarized excitation. The chiral fluid convection is induced by an asymmetric heat distribution generated by absorbed photons in the plasmonic heater. This concept can be potentially used to induce chiral fluid convection utilizing the chiral photothermal effect. Our proposed structure can potentially be used in various optofluidics applications related to biochemistry, clinical biology, and so on.

Which kind of feedback has a greater impact on individuals with social anxiety: facial or textual? An ERP study.

The present study is the first to compare the examined electrophysiological activity of facial and textual feedback of students with social anxiety after they finished a visual search task. Compared to textual feedback, facial feedback is much more effective. Specifically speaking, positive facial feedback caused stronger feedback-related negativity (FRN), and negative facial feedback caused late positive potential (LPP) of stronger amplitude. These changes in the FRN component (associated with feedback) and LPP (related to controlled attention engagement) provide clues about the interplay between anxiety and attention allocation in processing facial feedback. The results have implications for identifying the feedback format that will be most helpful for individuals with social anxiety.

Broadband chiral hybrid plasmon modes on nanofingernail substrates.

There is significant interest in the utility of asymmetric nanoaperture arrays as substrates for the surface-enhanced detection, fluorescence, and imaging of individual molecules. This work introduces obliquely-cut, out-of-plane, coaxial layered structures on an aperture edge. We refer to these structures as nanofingernails, which emphasizes their curved, oblique, and out-of-plane features. Broadband coupling into chiral hybrid plasmon modes and helicity-dependent near-field scattering without circular dichroism are demonstrated. The unusually-broadband, multipolar modes of nanofingernail micropore structures exhibit phase retardation effects that may be useful for achieving spatial overlap at different frequencies. The nanofingernail geometry shows new potential for simultaneous polarization-enhanced hyperspectral imaging on apertured, plasmonic surfaces.

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.

Plasmonic Chirality and Circular Dichroism in Bioassembled and Nonbiological Systems: Theoretical Background and Recent Progress.

Nature is chiral, thus chirality is a key concept required to understand a multitude of systems in physics, chemistry, and biology. The field of optics offers valuable tools to probe the chirality of nanosystems, including the measurement of circular dichroism, the differential interaction strength between matter and circularly polarized light with opposite helicity. Simultaneously, the use of plasmonic systems with giant light-interaction cross-sections opens new paths to investigate and manipulate systems on the nanoscale. Consequently, the interest in chiral plasmonic and hybrid systems has continually grown in recent years, due to their potential applications in biosensing, polarization-encoded optical communication, polarization-selective chemical reactions, and materials with polarization-dependent light-matter interaction. Experimentally, chiral properties of nanostructures can be either created artificially using modern fabrication techniques involving inorganic materials, or borrowed from nature using bioassembly or biomolecular templating. Herein, the recent progress in the field of plasmonic chirality is summarized, with a focus on both the theoretical background and the experimental advances in the study of chirality in various systems, including molecular-plasmonic assemblies, chiral plasmonic nanostructures, chiral assemblies of interacting plasmonic nanoparticles, and chiral metal metasurfaces and metamaterials. The growth prospects of this field are also discussed.

Active Far-Field Control of the Thermal Near-Field via Plasmon Hybridization.

The ability to control and manipulate temperature at nanoscale dimensions has the potential to impact applications including heat-assisted magnetic recording, photothermal therapies, and temperature-driven reactivity. One challenge with controlling temperature at nanometer dimensions is the need to mitigate heat diffusion, such that the temperature only changes in well-defined nanoscopic regions of the sample. Here we demonstrate the ability to use far-field laser excitation to actively shape the thermal near-field in individual gold nanorod heterodimers by resonantly pumping either the in-phase or out-of-phase hybridized dipole plasmon modes. Using single-particle photothermal heterodyne imaging, we demonstrate localization bias in the photothermal intensity due to preferential heating of one of the nanorods within the pair. Theoretical modeling and numerical simulation make explicit how the resulting photothermal images encode wavelength-dependent temperature biases between each nanorod within a heterodimer, demonstrating the ability to actively manage the thermal near-field by simply tuning the color of incident light.

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.

Optoelectronic Properties in Near-Infrared Colloidal Heterostructured Pyramidal "Giant" Core/Shell Quantum Dots.

Colloidal heterostructured quantum dots (QDs) are promising candidates for next-generation optoelectronic devices. In particular, "giant" core/shell QDs (g-QDs) can be engineered to exhibit outstanding optical properties and high chemical/photostability for the fabrication of high-performance optoelectronic devices. Here, the synthesis of heterostructured CuInSe x S2-x (CISeS)/CdSeS/CdS g-QDs with pyramidal shape by using a facile two-step method is reported. The CdSeS/CdS shell is demonstrated to have a pure zinc blend phase other than typical wurtzite phase. The as-obtained heterostructured g-QDs exhibit near-infrared photoluminescence (PL) emission (≈830 nm) and very long PL lifetime (in the microsecond range). The pyramidal g-QDs exhibit a quasi-type II band structure with spatial separation of electron-hole wave function, suggesting an efficient exciton extraction and transport, which is consistent with theoretical calculations. These heterostructured g-QDs are used as light harvesters to fabricate a photoelectrochemical cell, exhibiting a saturated photocurrent density as high as ≈5.5 mA cm-2 and good stability under 1 sun illumination (AM 1.5 G, 100 mW cm-2). These results are an important step toward using heterostructured pyramidal g-QDs for prospective applications in solar technologies.

Tunable Nonthermal Distribution of Hot Electrons in a Semiconductor Injected from a Plasmonic Gold Nanostructure.

For semiconductors photosensitized with organic dyes or quantum dots, transferred electrons are usually considered thermalized at the conduction band edge. This study suggests that the electrons injected from a plasmonic metal into a thin semiconductor shell can be nonthermal with energy up to the plasmon frequency. In other words, the electrons injected into the semiconductor are still hot carriers. Photomodulated X-ray absorption measurements of the Ti L2,3 edge are compared before and after excitation of the plasmon in Au@TiO2 core-shell nanoparticles. Comparison with theoretical predictions of the X-ray absorption, which include the heating and state-filling effects from injected hot carriers, suggests that the electrons transferred from the plasmon remain nonthermal in the ∼10 nm TiO2 shell, due in part to a slow trapping in defect states. By repeating the measurements for spherical, rod-like, and star-like metal nanoparticles, the magnitude of the nonthermal distribution, peak energy, and number of injected hot electrons are confirmed to be tuned by the plasmon frequency and the sharp corners of the plasmonic nanostructure. The results suggest that plasmonic photosensitizers can not only extend the sunlight absorption spectral range of semiconductor-based devices but could also result in increased open circuit voltages and elevated thermodynamic driving forces for solar fuel generation in photoelectrochemical cells.

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.

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.

Publisher Correction: Enhanced generation and anisotropic Coulomb scattering of hot electrons in an ultra-broadband plasmonic nanopatch metasurface.

The originally published version of this Article contained an error in Equation 1. The two ℏ terms were missing from this equation. This has now been corrected in the PDF and HTML versions of the Article.

Enhanced generation and anisotropic Coulomb scattering of hot electrons in an ultra-broadband plasmonic nanopatch metasurface.

The creation of energetic electrons through plasmon excitation of nanostructures before thermalization has been proposed for a wide number of applications in optical energy conversion and ultrafast nanophotonics. However, the use of "nonthermal" electrons is primarily limited by both a low generation efficiency and their ultrafast decay. We report experimental and theoretical results on the use of broadband plasmonic nanopatch metasurfaces comprising a gold substrate coupled to silver nanocubes that produce large concentrations of hot electrons, which we measure using transient absorption spectroscopy. We find evidence for three subpopulations of nonthermal carriers, which we propose arise from anisotropic electron-electron scattering within sp-bands near the Fermi surface. The bimetallic character of the metasurface strongly impacts the physics, with dissipation occurring primarily in the gold, whereas the quantum process of hot electron generation takes place in both components. Our calculations show that the choice of geometry and materials is crucial for producing strong ultrafast nonthermal electron components.The creation of energetic electrons through plasmon excitation has implications in optical energy conversion and ultrafast nanophotonics. Here, the authors find evidence for three subpopulations of nonthermal carriers which arise from anisotropic electron-electron scattering near the Fermi surface.