Metal telluride nanosheets by scalable solid lithiation and exfoliation.

Transition metal tellurides (TMTs) have been ideal materials for exploring exotic properties in condensed-matter physics, chemistry and materials science1-3. Although TMT nanosheets have been produced by top-down exfoliation, their scale is below the gram level and requires a long processing time, restricting their effective application from laboratory to market4-8. We report the fast and scalable synthesis of a wide variety of MTe2 (M = Nb, Mo, W, Ta, Ti) nanosheets by the solid lithiation of bulk MTe2 within 10 min and their subsequent hydrolysis within seconds. Using NbTe2 as a representative, we produced more than a hundred grams (108 g) of NbTe2 nanosheets with 3.2 nm mean thickness, 6.2 µm mean lateral size and a high yield (>80%). Several interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance, were observed that are generally restricted to highly crystalline MTe2 nanosheets. The TMT nanosheets also perform well as electrocatalysts for lithium-oxygen batteries and electrodes for microsupercapacitors (MSCs). Moreover, this synthesis method is efficient for preparing alloyed telluride, selenide and sulfide nanosheets. Our work opens new opportunities for the universal and scalable synthesis of TMT nanosheets for exploring new quantum phenomena, potential applications and commercialization.

Van der Waals polarity-engineered 3D integration of 2D complementary logic.

Vertical three-dimensional integration of two-dimensional (2D) semiconductors holds great promise, as it offers the possibility to scale up logic layers in the z axis1-3. Indeed, vertical complementary field-effect transistors (CFETs) built with such mixed-dimensional heterostructures4,5, as well as hetero-2D layers with different carrier types6-8, have been demonstrated recently. However, so far, the lack of a controllable doping scheme (especially p-doped WSe2 (refs. 9-17) and MoS2 (refs. 11,18-28)) in 2D semiconductors, preferably in a stable and non-destructive manner, has greatly impeded the bottom-up scaling of complementary logic circuitries. Here we show that, by bringing transition metal dichalcogenides, such as MoS2, atop a van der Waals (vdW) antiferromagnetic insulator chromium oxychloride (CrOCl), the carrier polarity in MoS2 can be readily reconfigured from n- to p-type via strong vdW interfacial coupling. The consequential band alignment yields transistors with room-temperature hole mobilities up to approximately 425 cm2 V-1 s-1, on/off ratios reaching 106 and air-stable performance for over one year. Based on this approach, vertically constructed complementary logic, including inverters with 6 vdW layers, NANDs with 14 vdW layers and SRAMs with 14 vdW layers, are further demonstrated. Our findings of polarity-engineered p- and n-type 2D semiconductor channels with and without vdW intercalation are robust and universal to various materials and thus may throw light on future three-dimensional vertically integrated circuits based on 2D logic gates.

Targeting foamy macrophages by manipulating ABCA1 expression to facilitate lesion healing in the injured spinal cord.

Spinal cord injury (SCI) triggers a complex cascade of events, including myelin loss, neuronal damage, neuroinflammation, and the accumulation of damaged cells and debris at the injury site. Infiltrating bone marrow derived macrophages (BMDMϕ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy Mϕ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy Mϕ and their potential implications for SCI. Contusion at T10 level of the spinal cord was induced using a New York University (NYU) impactor (5 g rod from a height of 6.25 mm) in male mice. ABCA1, an ATP-binding cassette transporter expressed by Mϕ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy Mϕ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy Mϕ as well as elevated pro-inflammatory response in vitro and in injured spinal cord. We also found that both genetic and pharmacological enhancement of ABCA1 expression accelerated lipid efflux from foamy Mϕ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy Mϕ, and accelerated clearance of cell debris and necrotic cells, which resulted in functional recovery. Our study highlights the importance of understanding the pathologic role of foamy Mϕ in SCI progression and the potential of ABCA1 as a therapeutic target for modulating the inflammatory response, promoting lipid metabolism, and facilitating functional recovery in SCI.

Carrier Transport Regulation of Pixel Graphene Transparent Electrodes for Active-Matrix Organic Light-Emitting Diode Display.

Integrating a graphene transparent electrode (TE) matrix with driving circuits is essential for the practical use of graphene in optoelectronics such as active-matrix organic light-emitting diode (OLED) display, however it is disabled by the transport of carriers between graphene pixels after deposition of a semiconductor functional layer caused by the atomic thickness of graphene. Here, the carrier transport regulation of a graphene TE matrix by using an insulating polyethyleneimine (PEIE) layer is reported. The PEIE forms an ultrathin uniform film (≤10 nm) to fill the gap of the graphene matrix, blocking horizontal electron transport between graphene pixels. Meanwhile, it can reduce the work function of graphene, improving the vertical electron injection through electron tunneling. This enables the fabrication of inverted OLED pixels with record high current and power efficiencies of 90.7 cd A-1 and 89.1 lm W-1 , respectively. By integrating these inverted OLED pixels with a carbon nanotube-based thin-film transistor (CNT-TFT)-driven circuit, an inch-size flexible active-matrix OLED display is demonstrated, in which all OLED pixels are independently controlled by CNT-TFTs. This research paves a way for the application of graphene-like atomically thin TE pixels in flexible optoelectronics such as displays, smart wearables, and free-form surface lighting.

Pushing the conductance and transparency limit of monolayer graphene electrodes for flexible organic light-emitting diodes.

Graphene has emerged as an attractive candidate for flexible transparent electrode (FTE) for a new generation of flexible optoelectronics. Despite tremendous potential and broad earlier interest, the promise of graphene FTE has been plagued by the intrinsic trade-off between electrical conductance and transparency with a figure of merit (σDC/σOp) considerably lower than that of the state-of-the-art ITO electrodes (σDC/σOp <123 for graphene vs. ∼240 for ITO). Here we report a synergistic electrical/optical modulation strategy to simultaneously boost the conductance and transparency. We show that a tetrakis(pentafluorophenyl)boric acid (HTB) coating can function as highly effective hole doping layer to increase the conductance of monolayer graphene by sevenfold and at the same time as an anti-reflective layer to boost the visible transmittance to 98.8%. Such simultaneous improvement in conductance and transparency breaks previous limit in graphene FTEs and yields an unprecedented figure of merit (σDC/σOp ∼323) that rivals the best commercial ITO electrode. Using the tailored monolayer graphene as the flexible anode, we further demonstrate high-performance green organic light-emitting diodes (OLEDs) with the maximum current, power and external quantum efficiencies (111.4 cd A-1, 124.9 lm W-1 and 29.7%) outperforming all comparable flexible OLEDs and surpassing that with standard rigid ITO by 43%. This study defines a straightforward pathway to tailor optoelectronic properties of monolayer graphene and to fully capture their potential as a generational FTE for flexible optoelectronics.

Fermi-Level Depinning in Metal/Ge Junctions by Inserting a Carbon Nanotube Layer.

Germanium (Ge)-based devices are recognized as one of the most promising next-generation technologies for extending Moore's law. However, one of the critical issues is Fermi-level pinning (FLP) at the metal/n-Ge interface, and the resulting large contact resistance seriously degrades their performance. The insertion of a thin layer is one main technique for FLP modulation; however, the contact resistance is still limited by the remaining barrier height and the resistance induced by the insertion layer. In addition, the proposed depinning mechanisms are also controversial. Here, the authors report a wafer-scale carbon nanotube (CNT) insertion method to alleviate FLP. The inserted conductive film reduces the effective Schottky barrier height without inducing a large resistance, leading to ohmic contact and the smallest contact resistance between a metal and a lightly doped n-Ge. These devices also indicate that the metal-induced gap states mechanism is responsible for the pinning. Based on the proposed technology, a wafer-scale planar diode array is fabricated at room temperature without using the traditional ion-implantation and annealing technology, achieving an on-to-off current ratio of 4.59 × 104 . This work provides a new way of FLP modulation that helps to improve device performance with new materials.

High-performance gold/graphene/germanium photodetector based on a graphene-on-germanium wafer.

The metal/germanium (Ge) photodetectors have attracted much attention for their potential applications in on-chip optoelectronics. One critical issue is the relatively large dark current due to the limited Schottky potential barrier height of the metal/germanium junction, which is mainly caused by the small bandgap of Ge and the Fermi energy level pinning effect between the metal and Ge. The main technique to solve this problem is to insert a thin interlayer between the metal and Ge. However, so far, the dark current of the photodetectors is still large when using a bulk-material insertion layer, while when using a two-dimensional insertion layer, the area of the insertion layer is too small to support a mass production. Here, we report a gold/graphene/germanium photodetector with a wafer-scale graphene insertion layer using a 4 inch graphene-on-germanium wafer. The insertion layer significantly increases the potential barrier height, leading to a dark current as low as 1.6 mA cm-2, and a responsivity of 1.82 A W-1which are the best results for metal/Ge photodetectors reported so far. Our work contributes to the mass production of high-performance metal/Ge photodetectors.

Flexible layer-structured Bi2Te3 thermoelectric on a carbon nanotube scaffold.

Inorganic chalcogenides are traditional high-performance thermoelectric materials. However, they suffer from intrinsic brittleness and it is very difficult to obtain materials with both high thermoelectric ability and good flexibility. Here, we report a flexible thermoelectric material comprising highly ordered Bi2Te3 nanocrystals anchored on a single-walled carbon nanotube (SWCNT) network, where a crystallographic relationship exists between the Bi2Te3 <[Formula: see text]> orientation and SWCNT bundle axis. This material has a power factor of ~1,600 µW m-1 K-2 at room temperature, decreasing to 1,100 µW m-1 K-2 at 473 K. With a low in-plane lattice thermal conductivity of 0.26 ± 0.03 W m-1 K-1, a maximum thermoelectric figure of merit (ZT) of 0.89 at room temperature is achieved, originating from a strong phonon scattering effect. The origin of the excellent flexibility and thermoelectric performance of the Bi2Te3-SWCNT material is attributed, by experimental and computational evidence, to its crystal orientation, interface and nanopore structure. Our results provide insight into the design and fabrication of high-performance flexible thermoelectric materials.

Macrodiversity Reception with Distributed Hard-Decision Receivers for Maritime Wireless Sensor Networks.

Maritime wireless sensor networks are considered to be the primary means of monitoring methods in the marine environment. The transmission between sensor node and sink node in maritime wireless sensor networks is usually unreliable due to the harsh propagation environment. To extend the transmission range or to enhance the transmission reliability between sensor nodes and sink node, we propose a macrodiversity reception scheme in the sink node equipped with distributed multiple hard-decision receivers. Multiple receivers are divided into several clusters and placed at different locations to receive different signal copies suffering from different fadings. Furthermore, a cascaded combining strategy based on hard-decision information is used to reduce the overall complexity of receiving side. The experimental results in the ocean scenarios show that the macrodiversity reception scheme with two antenna clusters has a transmission gain of 3-4 dB compared with the single antenna reception when the package loss rate is 10 - 2 . The study casts a new method for reliable transmission in maritime wireless sensor networks using commercial transceivers which can only output hard-decision results.

[Clinical features of children with severe adenovirus pneumonia and hemophagocytic syndrome: an analysis of 30 cases].

OBJECTIVE: To study the clinical features of children with severe adenovirus pneumonia (SAP) and hemophagocytic syndrome (HPS). METHODS: A retrospective analysis was performed from the chart review data of 30 children with SAP and HPS who were admitted from January 2014 to June 2019. According to the prognosis, the children were divided into a good prognosis group (n=18) and a poor prognosis group (n=12). RESULTS: Among the 30 children with SAP and HPS, the ratio of male to female was 2:1. The median age of onset was 1 year and 3 months (range 3 months to 5 years), and the mean course of fever was 19±7 d. Of the 30 children, 28 (93%) experienced disease onset in January to June. High-throughput gene detection of serum pathogens showed that 16 (53%) children were positive for human adenovirus type 7 (HAdV-7), and the other 14 (47%) children were positive for HAdV antigen based on immunofluorescence assay for throat swab, with unknown type. Of all 30 children, 29 (97%) had respiratory complications, 24 (80%) had cardiovascular complications, 16 (53%) had gastrointestinal complications, and 9 (30%) had toxic encephalopathy. Eighteen children (60%) improved or recovered and 12 (40%) did not recover (3 died). Compared with the good prognosis group, the poor prognosis group had a significantly longer course from onset to diagnosis of HPS (P<0.05), significantly higher levels of fibrinogen and tumor necrosis factor-α (P<0.05), and a significantly lower level of interferon-γ (P<0.05). The mean follow-up time was 6±2 months; 11 (41%) children recovered, 1 (4%) experienced recurrence of HPS, and 15 (56%) had the sequela of post-infectious bronchiolitis obliterans (PIBO). CONCLUSIONS: HPS may be observed in children with SAP, and PIBO is the most common sequela of SAP.

[Serum lipid profile in children with different subtypes of juvenile idiopathic arthritis].

OBJECTIVE: To study the serum lipid profile in children with different subtypes of juvenile idiopathic arthritis (JIA) during active and remission stages, as well as the long-term risk of atherosclerosis in children with JIA. METHODS: A total of 128 children newly diagnosed with active JIA were divided into oligoarticular JIA group with 48 children, polyarticular JIA group with 38 children, systemic JIA group with 22 children, and enthesitis-related JIA group with 20 children. According to the presence or absence of rheumatoid factor (RF), the polyarticular JIA group was further divided into RF-positive polyarticular JIA group with 15 children and RF-negative polyarticular JIA group with 23 children. A total of 45 children who underwent physical examination were randomly selected as healthy control group. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured and compared between groups. Blood lipid parameters were reexamined for 87 children in the remission stage after treatment and were compared with those in the active stage. RESULTS: Compared with the healthy control group, the systemic JIA group and the RF-positive polyarticular JIA group had a significant reduction in HDL-C and a significant increase in TG (P<0.05) in the active stage, while there were no significant differences in TC and LDL-C (P>0.05). There were no significant differences in blood lipid parameters between the other subtype JIA groups and the healthy control group (P>0.05). The RF-positive polyarticular JIA group had a significant increase in plasma HDL-C from the active stage to the remission stage (P<0.05), while the other subtype JIA groups had no significant changes in blood lipid parameters (P>0.05). CONCLUSIONS: Dyslipidemia may be observed in the active stage of children with systemic and RF-positive polyarticular JIA, with improvement in the remission stage of children with RF-positive polyarticular JIA. Further studies are needed to observe the long-term risk of atherosclerosis.

Unifying Terrain Awareness for the Visually Impaired through Real-Time Semantic Segmentation.

Navigational assistance aims to help visually-impaired people to ambulate the environment safely and independently. This topic becomes challenging as it requires detecting a wide variety of scenes to provide higher level assistive awareness. Vision-based technologies with monocular detectors or depth sensors have sprung up within several years of research. These separate approaches have achieved remarkable results with relatively low processing time and have improved the mobility of impaired people to a large extent. However, running all detectors jointly increases the latency and burdens the computational resources. In this paper, we put forward seizing pixel-wise semantic segmentation to cover navigation-related perception needs in a unified way. This is critical not only for the terrain awareness regarding traversable areas, sidewalks, stairs and water hazards, but also for the avoidance of short-range obstacles, fast-approaching pedestrians and vehicles. The core of our unification proposal is a deep architecture, aimed at attaining efficient semantic understanding. We have integrated the approach in a wearable navigation system by incorporating robust depth segmentation. A comprehensive set of experiments prove the qualified accuracy over state-of-the-art methods while maintaining real-time speed. We also present a closed-loop field test involving real visually-impaired users, demonstrating the effectivity and versatility of the assistive framework.

The prognostic role of abnormal liver function in IVIG unresponsiveness in Kawasaki disease: a meta-analysis.

OBJECTIVE: We aimed to assess the prognostic role of liver function alteration with intravenous immunoglobulin (IVIG) resistance in patients with Kawasaki disease (KD) by systematically analyzing and summarizing the results from published studies. METHODS: In this study, we summarized the evidence currently available up to March 31, 2015, and calculated the standard mean difference (SMD) of liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and total bilirubin between IVIG-responsive and IVIG-resistant patients. RESULTS: We found that the serum levels of these parameters in IVIG-non-responsive patients were significantly higher than that in IVIG-responsive group (total bilirubin: SMD = 0.984, 95%CI 0.712-1.184, p < 0.005; ALT: SMD = 0.555, 95%CI 0.400-0.710, p < 0.005; AST: SMD = 0.602, 95%CI 0.413-0.791, p < 0.005; GGT = 0.551, 95%CI 0.157-0.946, p = 0.006). There was evidence of heterogeneity (I (2) > 50%). The characteristics of patients could be the major sources, as analysis stratified by region significantly removed or reduced the heterogeneity. CONCLUSION: In summary, our meta-analysis suggested that liver abnormality was significantly associated with IVIG unresponsiveness in KD patients. Further study from more clinical investigations is needed to confirm this finding.

Elevated serum ghrelin, tumor necrosis factor-α and interleukin-6 in congenital heart disease.

BACKGROUND: The aim of this study was to investigate the association of congenital heart disease (CHD) with serum ghrelin, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. METHOD: Sixty-three children with CHD, hospitalized between January 2012 and September 2014 at Wuhan Women and Children's Health Care Center, were selected as the study group. Additionally, 28 healthy individuals who had physical examinations at this hospital were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum ghrelin, TNF-α and IL-6. SPSS 18.0 and Comprehensive Meta-analysis 2.0 were used for data analysis. RESULTS: There was significant difference in weight, height and body mass index (BMI; all P < 0.05) but not in age or sex (both P > 0.05) between the cyanotic CHD (CCHD), acyanotic CHD (ACHD) and control groups. On one-way analysis of variance serum ghrelin, TNF-α and IL-6 in both the CCHD and ACHD groups had a tendency to be higher compared with the control group (all P < 0.05), whereas, on Pearson correlation analysis, there was a correlation between serum ghrelin and BMI (all P < 0.05), and TNF-α was negatively, and IL-6 positively, correlated with BMI (all P < 0.05). Meta-analysis further demonstrated that serum ghrelin, TNF-α and IL-6 in both the CCHD and ACHD groups were higher than in the control group (all P < 0.05). CONCLUSION: Serum ghrelin, TNF-α and IL-6 are elevated in children with CHD, and may play a role in the development and progression of CHD.

Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris.

Macrophage activation and persistent inflammation contribute to the pathological process of spinal cord injury (SCI). It was reported that M2 macrophages were induced at 3-7 days after SCI but M2 markers were reduced or eliminated after 1 week. By contrast, M1 macrophage response is rapidly induced and then maintained at injured spinal cord. However, factors that modulate macrophage phenotype and function are poorly understood. We developed a model to distinguish bone-marrow derived macrophages (BMDMs) from residential microglia and explored how BMDMs change their phenotype and functions in response to the lesion-related factors in injured spinal cord. Infiltrating BMDMs expressing higher Mac-2 and lower CX3CR1 migrate to the epicenter of injury, while microglia expressing lower Mac-2 but higher CX3CR1 distribute to the edges of lesion. Myelin debris at the lesion site switches BMDMs from M2 phenotype towards M1-like phenotype. Myelin debris activates ATP-binding cassette transporter A1 (ABCA1) for cholesterol efflux in response to myelin debris loading in vitro. However, this homeostatic mechanism in injured site is overwhelmed, leading to the development of foamy macrophages and lipid plaque in the lesion site. The persistence of these cells indicates a pro-inflammatory environment, associated with enhanced neurotoxicity and impaired wound healing. These foamy macrophages have poor capacity to phagocytose apoptotic neutrophils resulting in uningested neutrophils releasing their toxic contents and further tissue damage. In conclusion, these data demonstrate for the first time that myelin debris generated in injured spinal cord modulates macrophage activation. Lipid accumulation following macrophage phenotype switch contributes to SCI pathology.

Highly Efficient Production of Cellulosic Ethanol from Poplar Using an Optimal C6/C5 Co-Fermentation Strain of Saccharomyces cerevisiae.

Cellulosic ethanol is the key technology to alleviate the pressure of energy supply and climate change. However, the ethanol production process, which is close to industrial production and has a high saccharification rate and ethanol yield, still needs to be developed. This study demonstrates the effective conversion of poplar wood waste into fuel-grade ethanol. By employing a two-step pretreatment using sodium chlorite (SC)-dilute sulfuric acid (DSA), the raw material achieved a sugar conversion rate exceeding 85% of the theoretical value. Under optimized conditions, brewing yeast co-utilizing C6/C5 enabled a yield of 35 g/L ethanol from 10% solid loading delignified poplar hydrolysate. We increased the solid loading to enhance the final ethanol concentration and optimized both the hydrolysis and fermentation stages. With 20% solid loading delignified poplar hydrolysate, the final ethanol concentration reached 60 g/L, a 71.4% increase from the 10% solid loading. Our work incorporates the pretreatment, enzymatic hydrolysis, and fermentation stages to establish a simple, crude poplar waste fuel ethanol process, expanding the range of feedstocks for second-generation fuel ethanol production.

A review of carbon nanotube- and graphene-based flexible thin-film transistors.

Carbon nanotubes (CNTs) and graphene have attracted great attention for numerous applications for future flexible electronics, owing to their supreme properties including exceptionally high electronic conductivity and mechanical strength. Here, the progress of CNT- and graphene-based flexible thin-film transistors from material preparation, device fabrication techniques to transistor performance control is reviewed. State-of-the-art fabrication techniques of thin-film transistors are divided into three categories: solid-phase, liquid-phase, and gas-phase techniques, and possible scale-up approaches to achieve realistic production of flexible nanocarbon-based transistors are discussed. In particular, the recent progress in flexible all-carbon nanomaterial transistor research is highlighted, and this all-carbon strategy opens up a perspective to realize extremely flexible, stretchable, and transparent electronics with a relatively low-cost and fast fabrication technique, compared to traditional rigid silicon, metal and metal oxide electronics.

[Changes in serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3, and their significance in children with left-to-right shunt congenital heart disease associated with heart failure].

OBJECTIVE: To investigate changes in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) and their significance in children with left-to-right shunt congenital heart disease (CHD) associated with heart failure (HF). METHODS: Twenty healthy children (control group), 20 children with HF, without basic heart disease (HF group), 20 children with left-to-right shunt CHD, without HF (CHD group), and 30 children with left-to-right shunt CHD associated with HF (CHD+HF group) were included in the study. These groups were compared in terms of serum IGF-1 and IGFBP-3 levels. According to the New York Heart Association (NYHA) Functional Classification, the CHD+HF group was further divided into NYHA-II, NYHA-III and NYHA-IV subgroups and the subgroups were compared in terms of serum IGF-1, IGFBP-3, and cardiac troponin I (cTnI) levels. The correlation of serum IGF-1 and IGFBP-3 levels with serum cTnI level in the CHD+HF group was analyzed. RESULTS: The CHD group showed decreased serum IGF-1 and IGFBP-3 levels compared with the control group (P<0.01). The CHD+HF group showed a significantly decreased serum IGF-1 level compared with the control group (P<0.01) and CHD group (P<0.05). The HF group had significantly increased serum IGF-1 and IGFBP-3 levels compared with other groups (P<0.01). The NYHA-II subgroup had the highest serum IGF-1 level and the NYHA-IV subgroup had the lowest serum IGF-1 level (P<0.01). In the CHD+HF group, serum IGF-1 and IGFBP-3 levels were negatively correlated with serum cTnI level (r=-0.692, P<0.05; r=-0.530, P<0.05). CONCLUSIONS: Serum IGF-1 level can be used as an objective condition evaluation indicator for CHD, and low serum IGF-1 level is a risk factor for HF. This also provides a clinical basis for treatment of HF using exogenous IGF-1.

Identification of a novel TNNI3 synonymous variant causing intron retention in autosomal recessive dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy type 2A (DCM2A, MIM: #611880) is a rare autosomal recessive heart disease leading to heart failure and sudden cardiac death. However, the causative role of TNNI3 in DCM2A is still questioned due to few cases reported and the conflicting molecular biological evidence. METHODS: Trio whole-exome sequencing (trio-WES) was performed in a Chinese family with dilated cardiomyopathy. Sanger sequencing and real-time quantitative PCR were used to confirm the variants identified. Expression outcome caused by the synonymous mutation was validated by minigene splicing analyses. RESULTS: The one-year-old girl presented severe left ventricular enlargement and significantly reduced left ventricular systolic function and she died of respiratory and heart failure soon after her diagnosis. Trio-WES revealed a compound heterozygous variants of TNNI3, a novel c.24G＞A (p.Ala8Ala) (NM_000363.4) in exon 2 and a deletion of entire gene. Minigene splicing analyses showed it led to an intron retention (c.24 + 1_24 + 45ins) by intron 2 cryptic splicing. CONCLUSIONS: Our study describes and characterizes a synonymous mutation in TNNI3 gene, supporting the clinical diagnosis of an autosomal recessive DCM. Our study emphasizes the importance of functional analysis to assess the potential pathogenicity of synonymous mutations, especially when the synonymous variants are not annotated as benign.

Sex Differences in Immune Cell Infiltration and Hematuria in SCI-Induced Hemorrhagic Cystitis.

Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic changes in the bladder. We analyzed the urine of male and female Sprague-Dawley and Fischer 344 rats after experimental spinal cord contusion, including unstained microscopic inspections of the urine, differential white blood cell counts colored by the Wright stain, and total leukocyte counts using fluorescent nuclear stains. We examined bladder histological changes in acute and chronic phases of SCI, using principal component analysis (PCA) and clustered heatmaps of Pearson correlation coefficients to interpret how measured variables correlated with each other. Male rats showed a distinct pattern of macroscopic hematuria after spinal cord injury. They had higher numbers of red blood cells with significantly more leukocytes and neutrophils than female rats, particularly hypersegmented neutrophils. The histological examination of the bladders revealed a distinct line of apoptotic umbrella cells and disrupted bladder vessels early after SCI and progressive pathological changes in multiple bladder layers in the chronic phase. Multivariate analyses indicated immune cell infiltration in the bladder, especially hypersegmented neutrophils, that correlated with red blood cell counts in male rats. Our study highlights a hitherto unreported sex difference of hematuria and pathological changes in males and females' bladders after SCI, suggesting an important role of immune cell infiltration, especially neutrophils, in SCI-induced hemorrhagic cystitis.