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Hirschsprung disease is characterized by the absence of enteric neurons caused by the defects of enteric neural crest cells, leading to intestinal obstruction. Here, using induced pluripotent stem cell-based models of Hirschsprung and single-cell transcriptomic analysis, we identify a gene set of 118 genes commonly dysregulated in all patient enteric neural crest cells, and suggest HDAC1 may be a key regulator of these genes. Furthermore, upregulation of RNA splicing mediators and enhanced alternative splicing events are associated with severe form of Hirschsprung. In particular, the higher inclusion rate of exon 9 in PTBP1 and the perturbed expression of a PTBP1-target, PKM, are significantly enriched in these patient cells, and associated with the defective oxidative phosphorylation and impaired neurogenesis. Hedgehog-induced oxidative phosphorylation significantly enhances the survival and differentiation capacity of patient cells. In sum, we define various factors associated with Hirschsprung pathogenesis and demonstrate the implications of oxidative phosphorylation in enteric neural crest development and HSCR pathogenesis.

Serial focussed ion beam scanning electron microscopy (FIB/SEM) enables imaging and assessment of subcellular structures on the mesoscale (10 nm to 10 µm). When applied to vitrified samples, serial FIB/SEM is also a means to target specific structures in cells and tissues while maintaining constituents’ hydration shells for in situ structural biology downstream. However, the application of serial FIB/SEM imaging of non-stained cryogenic biological samples is limited due to low contrast, curtaining, and charging artefacts. We address these challenges using a cryogenic plasma FIB/SEM. We evaluated the choice of plasma ion source and imaging regimes to produce high-quality SEM images of a range of different biological samples. Using an automated workflow we produced three-dimensional volumes of bacteria, human cells, and tissue, and calculated estimates for their resolution, typically achieving 20–50 nm. Additionally, a tag-free localisation tool for regions of interest is needed to drive the application of in situ structural biology towards tissue. The combination of serial FIB/SEM with plasma-based ion sources promises a framework for targeting specific features in bulk-frozen samples (>100 µm) to produce lamellae for cryogenic electron tomography.

Objective: Our primary objective was to determine whether pre-existing vulnerabilities and pandemic-related hardship resulted in cumulative (i.e., additive) versus compounding (i.e., multiplicative) effects on psychological distress in pregnant individuals during the COVID-19 pandemic. A secondary objective was to determine whether perceived social support and/or receipt of government financial aid buffered the effects of pandemic-related hardship on psychological distress.Method: Data are from a prospective pregnancy cohort study, the Pregnancy During the COVID-19 Pandemic study (PdP). This cross-sectional report is based upon the initial survey collected at recruitment between April 5, 2020 and April 30, 2021. Logistic regression was used to evaluate our objectives.Results: The data provide substantial evidence supporting a cumulative (additive) relationship between pandemic-related hardship and pre-existing vulnerabilities in relation to psychological distress. There was no evidence to support compounding (multiplicative) effects. Likewise, the buffering effect of social support was additive but not multiplicative. Government financial aid did not buffer the effects of objective hardship on psychological distress. Conclusion: Pre-pandemic vulnerability and pandemic-related hardship had cumulative effects on psychological distress during the COVID-19 pandemic. Adequate and equitable responses to pandemics and disasters may require more intensive supports for those with multiple vulnerabilities.

This study investigates whether the application of Hemopatch, a novel hemostatic patch, could prevent lymphatic leak after robotic-assisted radical prostatectomy (RARP) and bilateral pelvic lymph node dissection (BPLND). This is a prospective, single-center, phase III randomized controlled trial investigating the efficacy of Hemopatch in preventing lymphatic leak after RARP and BPLND. Participants were randomized to receive RARP and BPLND, with or without the use of Hemopatch, with an allocation ratio of 1:1. The primary outcome is the total drain output volume. The secondary outcomes include blood loss, operative time, lymph node yield, duration of drainage, drain output per day, hospital stay, transfusion and 30-day complications. A total of 32 patients were recruited in the study. The Hemopatch group had a significantly lower median total drain output than the control group (35 mL vs. 180 mL, p = 0.022) and a significantly lower drain output volume per day compared to the control group (35 mL/day vs. 89 mL/day, p = 0.038). There was no significant difference in the other secondary outcomes. In conclusion, the application of Hemopatch in RARP and BPLND could reduce the total drain output volume and the drain output volume per day. The use of Hemopatch should be considered to prevent lymphatic leakage after RARP and BPLND.

Hirschsprung disease (HSCR) is characterized by the absence of enteric neurons caused by the defects of enteric neural crest cells (ENCCs), leading to intestinal obstruction. Here, using iPSC-based models of HSCR and single-cell transcriptomic analysis, we identified a core gene set of 118 genes commonly dysregulated in all HSCR-ENCCs, with HDAC1 found to be a master regulator of these genes. Furthermore, upregulation of RNA splicing mediators and enhanced alternative splicing events were associated with severe form of HSCR. In particular, the higher inclusion rate of exon 9 in PTBP1 and the perturbed expression of a PTBP1-target, PKM, were significantly enriched in these HSCR-ENCCs, and associated with the defective oxidative-phosphorylation (OXPHOS) and impaired neurogenesis. Hedgehog-induced OXPHOS significantly enhanced the survival and differentiation capacity of HSCR-ENCCs. In sum, we have defined the core factors underpinning HSCR disease and demonstrated the implications of OXPHOS in ENCC development and HSCR pathogenesis.

Research Findings: This study evaluated the impacts of a bilingual Chinese-English reading program on Chinese children from low socioeconomic status (SES) families. Ninety-nine children in the thir...

Uniform Hf0.5Al0.5O top-gate (TG) dielectric can be grown directly on the MoS2 surface using a high/low-temperature deposition method, and excellent performances for few-layer (FL) MoS2 transistors with Hf0.5Al0.5O as TG dielectric can be achieved: high mobility of 90 cm2/Vs, small sub-threshold swing of 77 mV/dec and low interface-state density of $1.08\times {10}^{{12}}$ eV−1cm−2. The involved mechanisms lie in the facts that (1) the TG dielectric can prevent the MoS2 surface from absorbing the oxygen and moisture in the air; (2) growing the Hf0.5Al0.5O dielectric at low temperature can well provide nucleation sites for its subsequent high-temperature growth; and (3) doping Al into HfO2 can reduce the trap charges in the resulting HfAlO dielectric to weaken the Coulomb scattering and also produce densified and uniform dielectric film. Therefore, the Hf0.5Al0.5O TG-dielectric structure and its growth method described in this work have a high potential to fabricate high-performance FL MoS2 field-effect transistors for practical electron device applications.

Amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs) with HfLaO as high-k gate dielectric have been fabricated, and p-type silicon wafers with resistivities of 0.001 ~ 0.002, 0.005, 0.02 ~ 0.021 and $5\sim 10\Omega \cdot $ cm are used as their gate electrodes. The carrier mobility of the samples show an increase with increasing gate acceptor concentration, indicating that the TFT performances are affected by the hole concentration in the gate electrode. The HfLaO gate dielectric is highly polarizable and so produces surface-optical phonons, which can scatter the electrons in the IGZO channel to reduce their mobility. Therefore, this work directly demonstrates that the holes in the gate electrode can have a screening effect to suppress this remote phonon scattering of the gate dielectric on the channel carriers, just like the electrons in the metal gate, ITO gate and n-silicon gate of field-effect transistors.

Ge-based MOS capacitor with HfTiON/(LaON/Si) gate stacks and fluorine-plasma treatment (FPT) has been well investigated by transmission electron microscopy (TEM), electrical measurements and X-ray photoemission spectroscopy (XPS) in this work. Electrical measurements have shown that fluorine-plasma treated Ge MOS capacitor exhibits negligible hysteresis (15 mV), small gate leakage current (3.66 × 10−6 A/cm2 at Vfb + 1 V), and low interface-state density at midgap (3.2 × 1011 cm−2 eV−1). TEM results indicate that high quality LaSiON/Ge interfaces. XPS results further reveal the presence of fluorine incorporation and the less content of the Ge oxides at the LaSiON/Ge interface. These improvements should be attributed to the LaSiON passivation layer and FPT can suppress the formation of volatile and unstable Ge oxides. In addition, LaSiON passivation layer can further block inter-diffusion of elements between HfTiON and Ge substrate, and FPT can occupy the oxygen vacancies and reduce interface traps in the HfTiON dielectric and LaSiON/Ge interface. These greatly improve the performance of the Ge MOS device.

The effects of treating the HfO2 gate dielectric in different plasmas (O2, N2, and NH3) on the electrical characteristics of a back-gated MoS2 transistor are investigated. It is found that the electrical properties of the device improved after HfO2 is treated by these plasmas, in which NH3-plasma treatment results in the best electrical characteristics: high ON–OFF ratio of $1.26\times 10^{{7}}$ , high extrinsic carrier mobility of 61.5 cm2/ $\text{V}\cdot \text{s}$ , small subthreshold swing (SS) of 111 mV/dec, low interface-state density of $2.79\times 10^{12}$ eV $^{-{1}}\,\,\cdot $ cm−2, and small hysteresis of 43 mV. These should be attributed to the incorporation of more N into the HfO2 film by the NH3 plasma to repair the oxygen vacancies and increase the $k$ value of the HfO2 film. Moreover, H from the NH3 plasma effectively passivates the dangling bonds at/near the HfO2/MoS2 interface, thus creating an excellent MoS2/HfO2 interface.

The caries prevalence among Singapore children remains high, with almost 50% affected by the age of 6 years. Among oral hygiene homecare, toothpastes with a minimum fluoride concentration of 1000 ppm or greater have been shown to be more effective at preventing caries. Previous concerns with dental fluorosis have led to the marketing of non-fluoride and low-fluoride toothpastes specifically for children. In the local context, many parents start their children on these products due to ingestion concerns and recommendations of the product, rather than on sound advice from a healthcare professional. The latest recommendation is to use a smear size of 1000 ppm or greater fluoride toothpaste in children under 3 years of age with high caries risk. For children aged 3 years and older, a pea size of 1000 ppm or greater fluoride toothpaste should be used. As medical physicians are typically the first healthcare encounter for many children, they are well positioned to provide recommendations on the concentration and amount of fluoride toothpaste to be used in young children.

Background: Fetal growth restriction (FGR) is a major risk factor for bronchopulmonary dysplasia (BPD). Maternal stress and poor diet are linked to FGR. Effect of perinatal stress on lung development remains unknown. Objective: Using a murine model of adverse early life environment (AELE), we hypothesized that maternal exposure to perinatal environmental stress and high-fat diet (Western diet) lead to impaired lung development in the offspring. Methods: Female mice were placed on either control diet or Western diet before conception. Those exposed to Western diet were also exposed to perinatal environmental stress, the combination referred to as AELE. Pups were either euthanized at postnatal day 21 (P21) or weaned to control diet and environment until adulthood (8–14 wk old). Lungs were harvested for histology, gene expression by quantitative RT-PCR, microRNA profiling, and immunoblotting. Results: AELE increased the mean linear intercept and decreased the radial alveolar count and secondary septation in P21 and adult mice. Capillary count was also decreased in P21 and adult mice. AELE lungs had decreased vascular endothelial growth factor A (VEGFA), VEGF receptor 2, endothelial nitric oxide synthase, and hypoxia inducible factor-1α protein levels and increased expression of genes that regulate DNA methylation and upregulation of microRNAs that target genes involved in lung development at P21. Conclusion: AELE leads to impaired lung alveolar and vascular growth, which persists into adult age despite normalizing the diet and environment at P21. AELE also alters the expression of genes involved in lung remodeling.

We report an experiment using a vibrating needle to activate calcium ions and waves in mice muscle tissue fibers. In vivo Ca2+ migration in mice was observed along with its muscle pathways using two-photon laser fluorescence.

ALD Al2O3 films treated respectively by N2, O2 and NH3 plasmas are used as gate dielectrics to fabricate few-layered MoS2 FETs. As compared with the control sample without any plasma treatment, the devices with different plasmas treatments achieve better electrical properties, with the NH3-treated device having the best results: highest carrier mobility of 39.3 cm2/Vs (~1.65 times higher than that of the control sample), smallest subthreshold swing of 90.9 mV/dec, largest on/off ratio of 1.5 × 107 and negligible hysteresis. These are attributed to the fact that the NH3 plasma treatment can (1) effectively passivate the oxygen vacancies in Al2O3 and decrease the dangling bonds at the Al2O3 surface, thus reducing the traps at/near the Al2O3/MoS2 interface; (2) increase the k value of the dielectric by N incorporation to enhance the screening effect on the Coulomb impurity scattering. In addition, these plasma treatments can adjust the MoS2 FET from depletion mode to enhancement mode by introducing negative ions into the gate dielectric.

Bottom-gated pentacene organic thin-film transistors (OTFTs) were fabricated on p-type and n-type Si wafers with different resistivities, with NdTaON as a high- ${k}$ gate dielectric. Although the pentacene grain size and dielectric surface roughness were nearly the same for all the samples, the carrier mobility improved with decreasing resistivity for both types of OTFTs (p-gate and n-gate), indicating that similar to the electron concentration, the hole concentration in the gate electrode can also affect the carrier mobility. This is attributed to the remote phonon scattering of the high- ${k}$ gate dielectric on the channel carriers, which can be screened by the holes in the gate electrode. The p-gate and n-gate samples with the lowest gate–electrode resistivity of $0.005~\Omega \cdot $ cm achieve the highest mobility of 1.15 and 1.37 cm $^{{2}}/\text{V}\cdot \text{s}$ , respectively. Moreover, for the same gate-doping concentration, the p-gate sample shows lower mobility than the n-gate sample. This is likely because under a negative gate voltage ( ${V}_{g}$ ), the p-gate is depleted to make the actual ${V}_{g}$ smaller than the applied ${V}_{g}$ , thus resulting in a lower extracted carrier mobility. In addition, such a depletion effect leads to a lower hole concentration near the gate–electrode/gate–dielectric interface, thus weakening the gate screening effect on the remote phonon scattering.

The effects of trapped charges in gate dielectric and high- ${k}$ encapsulation layer on the performance of MoS2 transistor are investigated by using SiO2 with different thicknesses as the gate dielectric and HfO2 as the encapsulation layer of the MoS2 surface. Results indicate that the positive trapped charges in SiO2 can increase the electrons in MoS2 for screening the scattering of charged impurity (CI) in SiO2 and at the SiO2/MoS2 interface to increase the carrier mobility. However, the CI scattering becomes stronger for thicker gate dielectric with more trapped charges and can dominate the electron screening effect to reduce the mobility. On the other hand, with the HfO2 encapsulation, the OFF-currents of the devices greatly increase and their threshold voltages shift negatively due to more electrons induced by more positive charges trapped in HfO2. Moreover, the screening effect of these electrons on the CI scattering results in a mobility increase, which increases with the magnitude of the CI scattering. A 51% improvement in mobility is obtained for the sample suffering from the strongest CI scattering, fully demonstrating the effective screening role of high- ${k}$ dielectric on the CI scattering.

In order to improve the hygroscopic property of LaON and also maintain its excellent interface quality with Ge, LaON incorporated with Ta is proposed and its hygroscopic and electrical properties are investigated by using dry and wet annealing. It is found that large improvement in hygroscopic property can be obtained by the Ta incorporation, and also the LaTaON film exhibits excellent interface quality with the Ge substrate due to the capability of TaON in blocking elemental inter-diffusions and also the passivation effect of LaGeOxNy formed at the LaTaON/Ge interface. Therefore, LaTaON can be considered as a high-quality gate dielectric in Ge MOS device to achieve excellent interfacial and electrical properties, e.g. in this work: high k value (21.0), low interface-state density (5.94 × 1011 cm−2 eV−1), low gate leakage current (3.07 × 10−4 A/cm2 at Vg = Vfb + 1 V) and high resistance against moisture absorption.

Bottom-gated pentacene organic thin-film transistors with LaTiON gate dielectrics annealed at two different temperatures are fabricated on n+Si wafers. Although atomic-force microscopyresults indicate a smoother dielectric surface and larger pentacene grains for the sample annealed at 400 °C, this sample shows lower carrier mobility than the one annealed at 200 °C. Moreover, the crystallinity of the gate dielectrics is not a key factor in the degradation of the carrier mobility because both dielectrics remain amorphous according to TEM. However, the TEM results show that the sample annealed at 400 °C has a thicker dielectric/Si-gate interlayer. The resultant increase in gate electrode-to-dielectric distance weakens the gate screening of the remote phonon scattering, thereby degrading the mobility of the carriers in the pentacene channel. This effect can be further supported by two similar samples fabricated on n-Si wafers, in which the gate electrode with lower electron concentration has a reduced screening effect on the remote phonon scattering and results in a larger reduction in mobility for the 400 °C-annealed sample with thicker interlayer.

In this work, the ferroelectricity of hafnium zirconium oxide (Hf