Cataract-causing Y204X mutation of crystallin protein CRYßB1 promotes its C-terminal degradation and higher-order oligomerization.

Crystallin proteins are a class of main structural proteins of the vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode these crystallin proteins is the most common cause for congenital cataracts. Despite extensive studies, the pathogenic and molecular mechanisms that effect congenital cataracts remain unclear. In this study, we identified a novel mutation in CRYBB1 from a congenital cataract family, and demonstrated that this mutation led to an early termination of mRNA translation, resulting in a 49-residue C-terminally truncated CRYßB1 protein. We show this mutant is susceptible to proteolysis, which allowed us to determine a 1.2-Å resolution crystal structure of CRYßB1 without the entire C-terminal domain. In this crystal lattice, we observed that two N-terminal domain monomers form a dimer that structurally resembles the WT monomer, but with different surface characteristics. Biochemical analyses and cell-based data also suggested that this mutant is significantly more liable to aggregate and degrade compared to WT CRYßB1. Taken together, our results provide an insight into the mechanism regarding how a mutant crystalin contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in protein aggregation.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

Molecular design, construction and analgesic mechanism insights into the novel transdermal fusion peptide ANTP-BgNPB.

Toad venom, a traditional Chinese medicine, exhibits remarkable medicinal properties of significant therapeutic value. The peptides present within toad venom possess a wide range of biological functions, yet the neuropeptide B (NPB) and it modification requires further exploration to comprehensively understand its mechanisms of action and potential applications. In this study, a fusion peptide, ANTP-BgNPB, was designed to possess better analgesic properties through the transdermal modification of BgNPB. After optimizing the conditions, the expression of ANTP-BgNPB was successfully induced. The molecular dynamics simulations suggested that the modified protein exhibited improved stability and receptor binding affinity compared to its unmodified form. The analysis of the active site of ANTP-BgNPB and the verification of mutants revealed that GLN3, SER38, and ARG42 were crucial for the protein's recognition and binding with G protein-coupled receptor 7 (GPR7). Moreover, experiments conducted on mice using the hot plate and acetic acid twist body models demonstrated that ANTP-BgNPB was effective in transdermal analgesia. These findings represent significant progress in the development of transdermal delivery medications and could have a significant impact on pain management.

Processing bulk natural wood into a high-performance structural material.

Synthetic structural materials with exceptional mechanical performance suffer from either large weight and adverse environmental impact (for example, steels and alloys) or complex manufacturing processes and thus high cost (for example, polymer-based and biomimetic composites). Natural wood is a low-cost and abundant material and has been used for millennia as a structural material for building and furniture construction. However, the mechanical performance of natural wood (its strength and toughness) is unsatisfactory for many advanced engineering structures and applications. Pre-treatment with steam, heat, ammonia or cold rolling followed by densification has led to the enhanced mechanical performance of natural wood. However, the existing methods result in incomplete densification and lack dimensional stability, particularly in response to humid environments, and wood treated in these ways can expand and weaken. Here we report a simple and effective strategy to transform bulk natural wood directly into a high-performance structural material with a more than tenfold increase in strength, toughness and ballistic resistance and with greater dimensional stability. Our two-step process involves the partial removal of lignin and hemicellulose from the natural wood via a boiling process in an aqueous mixture of NaOH and Na2SO3 followed by hot-pressing, leading to the total collapse of cell walls and the complete densification of the natural wood with highly aligned cellulose nanofibres. This strategy is shown to be universally effective for various species of wood. Our processed wood has a specific strength higher than that of most structural metals and alloys, making it a low-cost, high-performance, lightweight alternative.

Mask, the Drosophila ankyrin repeat and KH domain-containing protein, affects microtubule stability.

Proper regulation of microtubule (MT) stability and dynamics is vital for essential cellular processes, including axonal transportation and synaptic growth and remodeling in neurons. In the present study, we demonstrate that the Drosophila ankyrin repeat and KH domain-containing protein Mask negatively affects MT stability in both larval muscles and motor neurons. In larval muscles, loss-of-function of mask increases MT polymer length, and in motor neurons, loss of mask function results in overexpansion of the presynaptic terminal at the larval neuromuscular junctions (NMJs). mask genetically interacts with stathmin (stai), a neuronal modulator of MT stability, in the regulation of axon transportation and synaptic terminal stability. Our structure-function analysis of Mask revealed that its ankyrin repeats domain-containing N-terminal portion is sufficient to mediate Mask's impact on MT stability. Furthermore, we discovered that Mask negatively regulates the abundance of the MT-associated protein Jupiter in motor neuron axons, and that neuronal knocking down of Jupiter partially suppresses mask loss-of-function phenotypes at the larval NMJs. Taken together, our studies demonstrate that Mask is a novel regulator for MT stability, and such a role of Mask requires normal function of Jupiter.

Iron overload facilitates neonatal hypoxic-ischemic brain damage via SLC7A11-mediated ferroptosis.

Oxidative damage and cell death are involved in the pathogenesis of hypoxic-ischemic brain damage (HIBD). Ferroptosis is a newly identified mode of cell death that results from the oxidative damage induced by excessive iron. In HIBD, iron accumulates in brain tissues due to the massive destruction of red blood cells and increased permeability of the blood brain barrier vasculature, which can trigger ferroptosis. Ferroptosis is implicated in various diseases involving neuronal injury; however, the roles of iron and ferroptosis in HIBD have not been identified. In the present study, we investigated the role of iron overload in neuronal ferroptosis both in HIBD rat models and in oxygen- and glucose-deprived (OGD) SH-SY5Y cells. We observed that iron deposition in the cerebral cortex was significantly increased in HIBD rats. Features of ferroptosis such as shrunken mitochondria, increased MDA (malondialdehyde) levels, and reduced solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression were observed in the cerebral cortex of HIBD rats. Administration of an iron chelator in HIBD rats upregulated SLC7A11 expression and alleviated neuronal ferroptosis in cerebral cortex tissue. Additionally, overexpression of SLC7A11 in SH-SY5Y cells increased cell viability and attenuated OGD-induced ferroptosis. Our results demonstrate that iron overload induces neuronal ferroptosis by inhibiting SLC7A11 expression in HIBD. Inhibition of neuronal ferroptosis may be a promising strategy to alleviate brain damage in HIBD.

Triptonide inhibits growth and metastasis in HCC by suppressing EGFR/PI3K/AKT signaling.

Liver cancer represents one of the deadliest cancers, with a rising incidence worldwide. Triptonide is found in the traditional Chinese medicinal plant Tripterygium wilfordii Hook. This study aimed to examine the anticancer properties of triptonide in human hepatocellular carcinoma (HCC). HCC cells were administered with triptonide at various levels, and CCK-8 and colony formation assays were carried out for detecting HCC cell proliferation. Then, cell apoptosis and cell cycle distribution were evaluated by flow cytometry. Tumor growth was monitored noninvasively by ultrasound imaging. Cell migration and invasion were quantitated by wound healing and Transwell assays. A metastasis model was established via tail vein injection of HCC cells in nude mice. Immunoblot was performed to quantitate the expression of proteins involved in the EGFR/PI3K/AKT signaling and its downstream effectors. Triptonide repressed cell proliferation and induced cell cycle arrest and apoptosis in cultured HCC cells, and suppressed tumor growth in vivo. In addition, triptonide inhibited EMT, migration and invasion in cultured HCC cells, and lung metastasis in nude mice. Mechanistically, triptonide acted by inhibiting the EGFR/PI3K/AKT signaling and regulated its downstream effectors, e.g., the cell cycle-associated protein cyclin D1, the apoptosis-related protein Bcl-2, the EMT marker E-cadherin, and the invasion-related protein MMP-9. Triptonide suppresses proliferation, EMT, migration and invasion, and promotes apoptosis and cell cycle arrest by repressing the EGFR/PI3K/AKT signaling. Therefore, triptonide might be considered for liver cancer treatment.

Development and Assessment of Assisted Diagnosis Models Using Machine Learning for Identifying Elderly Patients With Malnutrition: Cohort Study.

BACKGROUND: Older patients are at an increased risk of malnutrition due to many factors related to poor clinical outcomes. OBJECTIVE: This study aims to develop an assisted diagnosis model using machine learning (ML) for identifying older patients with malnutrition and providing the focus of individualized treatment. METHODS: We reanalyzed a multicenter, observational cohort study including 2660 older patients. Baseline malnutrition was defined using the global leadership initiative on malnutrition (GLIM) criteria, and the study population was randomly divided into a derivation group (2128/2660, 80%) and a validation group (532/2660, 20%). We applied 5 ML algorithms and further explored the relationship between features and the risk of malnutrition by using the Shapley additive explanations visualization method. RESULTS: The proposed ML models were capable to identify older patients with malnutrition. In the external validation cohort, the top 3 models by the area under the receiver operating characteristic curve were light gradient boosting machine (92.1%), extreme gradient boosting (91.9%), and the random forest model (91.5%). Additionally, the analysis of the importance of features revealed that BMI, weight loss, and calf circumference were the strongest predictors to affect GLIM. A BMI of below 21 kg/m2 was associated with a higher risk of GLIM in older people. CONCLUSIONS: We developed ML models for assisting diagnosis of malnutrition based on the GLIM criteria. The cutoff values of laboratory tests generated by Shapley additive explanations could provide references for the identification of malnutrition. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-EPC-14005253; https://www.chictr.org.cn/showproj.aspx?proj=9542.

[Analysis of a case of Multiple pterygium syndrome due to a novel variant of CHRNG gene].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION: The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.

Ultra-broadband and completely modulated absorption enhancement of monolayer graphene in a near-infrared region.

Achieving ultra-broadband and completely modulated absorption enhancement of monolayer graphene in near-infrared region is practically important to design graphene-based optoelectronic devices, however, which remains a challenge. In this work, by spectrally designing multiple magnetic plasmon resonance modes in metamaterials to be adjacent to each other, near-infrared light absorption in monolayer graphene is greatly improved to have an averaged absorption efficiency exceeding 50% in a very broad absorption bandwidth of about 800 nm. Moreover, by exerting an external bias voltage on graphene to change Fermi energy of graphene, the ultra-broadband absorption enhancement of monolayer graphene exhibits an excellent tunability, which has a nearly 100% modulation depth and an electrical switching property. This work is promising for applications in near-infrared photodetectors, amplitude modulators of electromagnetic waves, etc.

Finding point method and re-optimized method for the brightness temperature simulation from Fengyun 4A AGRI in infrared channels.

The correlated k-distribution (CKD) is a fast radiative transfer model and is often used in atmospheric absorption simulation. In the paper, we apply two automatic CKD methods to satellite brightness temperature simulations from the Fengyun 4A Advanced Geostationary Radiation Imager (AGRI) in infrared channels, namely, the finding point method (FPM) and the re-optimized method (ROM). In the calculation, we used Radiative Transfer for the Television Observation Satellite Operational Vertical Sounder (RTTOV) as the comparison, and we use line-by-line (LBL) integration as the reference. Compared with LBL in the brightness temperature simulation of real profiles, the errors of FPM in 7.1 µm and 13.5 µm channels are 0.22 K, -0.13K for mean error and 0.3128 K, 0.2184 K for root mean square error (RMSE), respectively, which are larger than that of RTTOV, with 0.16 K, 0.02 K, 0.2144 K, and 0.1226 K, respectively. In the other channels, the results show that of ROM has the highest accuracy and RTTOV has the lowest accuracy. In general, FPM and ROM can achieve very good accuracy in satellite infrared remote sensing.

Trimodal prehabilitation for older surgical patients: a systematic review and meta-analysis.

OBJECTIVE: To determine the postoperative effectiveness of trimodal prehabilitation in older surgical patients. METHODS: We searched Medline, PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for observational cohort studies and randomised controlled trials (RCTs) of older surgical patients who underwent trimodal prehabilitation. We performed a meta-analysis to estimate the pooled risk ratio (RR) for dichotomous data and weighted mean difference (MD) for continuous data. Primary outcomes were postoperative mortality and complications, and the secondary outcomes were the 6-min walk test (6MWT) at 4 and 8 weeks after surgery, readmission, and length of hospital stay (LOS). This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42020201347). RESULTS: We included 10 studies (four RCTs and six cohort studies) comprising 1553 older surgical patients (trimodal prehabilitation group, n = 581; control group, n = 972). There were no significant differences in postoperative mortality (RR 1.32; 95% confidence interval [CI] 0.52-3.35) and postoperative complications (RR 0.91; 95% CI 0.76-1.09). Prehabilitation did not reduce readmission (RR 0.92; 95% CI 0.61-1.38) and LOS (MD 0.10; 95% CI - 0.34-0.53). In a sub-analysis, trimodal prehabilitation did not significantly improve postoperative mortality, postoperative complications, readmission rates, or LOS when compared with standard care. However, trimodal prehabilitation significantly improved the 6MWT at 4 weeks after surgery (MD 37.49; 95% CI 5.81-69.18). CONCLUSIONS: Our systematic review and meta-analysis demonstrated that trimodal prehabilitation did not reduce postoperative mortality and complications significantly but improved postoperative functional status in older surgical patients. Therefore, more high-quality trials are required.

Malnutrition dynamics according to GLIM criteria in hospitalized elderly.

BACKGROUND AND OBJECTIVES: Assess the different nutritional status between admission and discharged in older adult patients using the GLIM criteria. METHODS AND STUDY DESIGN: A retrospective analysis was conducted on a multicenter study which initiated in 34 hospitals in China with 2734 hospitalized older patients. The dynamic changes of malnutrition according to GLIM criteria were performed between at admission and discharge, and their significance was analyzed using the chi-square test. The association between malnutrition and clinical outcomes was analyzed using the chi-square test, t-test, or rank sum test, and divided into different disease types for further analysis. RESULTS: The incidence of nutritional risk in elderly patients was 51.6% at admission and 48.4% at discharge. The prevalence of malnutrition according to the GLIM criteria was 19.6% at admission and increased to 33.4% at discharge, which was significantly different. Different age and disease type were related with nutrition status. Malnutrition is significantly association with adverse clinical outcomes such as increased risk of complications and prolonged length of hospital stay. CONCLUSIONS: The GLIM criteria can be used in elderly patients to assess malnutrition. The prevalence of malnutrition in elderly inpatients is high, and the prevalence of malnutrition at discharge is higher than that observed at admission. Attention should be paid to the dynamic changes of malnutrition in elderly patients during hospitalization.

Generative Adversarial Network of Industrial Positron Images on Memory Module.

PET (Positron Emission Computed Tomography) imaging is a challenge due to the ill-posed nature and the low data of photo response lines. Generative adversarial networks have been widely used in computer vision and made great success recently. In our paper, we trained an adversarial model to improve the industrial positron images quality based on the attention mechanism. The innovation of the proposed method is that we build a memory module that focuses on the contribution of feature details to interested parts of images. We use an encoder to get the hidden vectors from a basic dataset as the prior knowledge and train the nets jointly. We evaluate the quality of the simulation positron images by MS-SSIM and PSNR. At the same time, the real industrial positron images also show a good visual effect.

Case Report of a pathologically confirmed vascular parkinsonism with early cognitive impairment and Behavioral disturbance.

BACKGROUND: Vascular Parkinsonism(VaP) is defined as parkinsonism resulting from cerebral vascular disease(CVD), with presence of variable motor and non-motor signs that are corroborated by clinical, anatomic or imaging findings of cerebrovascular disease. Overlapping syndromes with mixed pathologies make VaP difficult to distinguish from primary neurodegenerative parkinsonism.To understand the clinical and pathological features of VaP,we report a case of autopsy confirmed vascular Parkinsonism that was clinical misdiagnosed as idiopathic Parkinson's disease.Clinical features include early mixed symptoms of dementia,behavioral disturbance and parkinsonism that were similar to Dementia with lewy Body(DLB) and Parkinson disease Dementia(PDD). CASE PRESENTATION: A 84-year-old man presented progressive parkinsonism with prominent postural instability, gait impairment, pseudobulbar, early cognitive impairment, irritability, hallucination, urinary symptoms and poor responsiveness to dopaminergic drugs. He was clinically diagnosed as Parkinson disease(PD). In the post-mortem study, we examined Aß and phospho-tau as pathological biomarker for Alzheimer's disease(AD), α-synucleing in medulla, pons and midbrain for PD and DLB. Hematoxylin and eosin staining in cerebral cortex, cerebellum and brainstem examines vascular pathological changes and microvascular lesion.Neither Lewy bodies in the substantia nigra ,locus ceruleus and cerebrumnor accumulation of Aß, neurofibrillary tangles were noted. Instead, there were many cerebral infarctions and widespread arteriosclerosis in the brain. The final brain autopsy supported a diagnosis of VaP not PD. CONCLUSIONS: This case of pathologically confirmed VaP misdiagnosed as idiopathic PD suggested that we must be vigilant about the possibility of VaP for patients with parkinsonisms, cognitive impairments, early behavioral and psychological symptoms,imaging performances of cerebral small vessel disease and other vascular damages.

Plasmonic dye-sensitized solar cells through collapsible gold nanofingers.

Plasmonic nanostructures are successfully demonstrated in solar cells due to their broad spectra-selective resonance in the range of ultraviolet to near-infrared, and thus light absorption can be mostly improved and power conversion efficiency (PCE) further. Here, we demonstrate plasmonic dye-sensitized solar cells (DSSCs) using collapsible Au nanofingers to build photoanode to enhance light absorption. In this plasmonic DSSCs, by balancing local field enhancement due to gap-plasmon resonance and dye fluorescence quenching, the optimal gap size in collapsed Au/Al2O3/Au nanofingers is designed by twice the Al2O3thickness and then deposited a TiO2layer as photoanode. The results show that the PCE of DSSCs is mostly improved as compared to DSSCs with photoanode of Au/Al2O3/TiO2films, which can be ascribed to the coupled local field enhancement within the sub-nanometer gaps. In addition, fluorescence of dyes on plasmonic nanofingers is nearly 10 times higher than plain Au/Al2O3/TiO2films, which further proves the dye absorption enhancement. These plasmonic nanofingers enable the precise engineering of gap-plasmon modes and can be scaled up to wafer scale with low cost by the nanoimprint lithography technique, which suggests the feasibility of applying our result in constructing the photoanode for other types of solar cells.

Homoharringtonine inhibits the progression of hepatocellular carcinoma by suppressing the PI3K/AKT/GSK3ß/Slug signaling pathway.

Homoharringtonine (HHT), was first isolated from the bark of Cephalotaxus harringtonia (Knight ex J. Forbes) K. Koch and Cephalotaxus fortunei Hook trees. The bark extract is used to treat leukemia and in recent years has also been used in traditional Chinese medicine (TCM) to treat solid tumors. However, the inhibitory mechanism of HHT in the progression of hepatocellular carcinoma (HCC) is rarely studied. We aimed to evaluate the antitumor efficacy of HHT on HCC in vitro and in vivo and elucidate the underlying molecular mechanism(s). HCC cell lines, including HCCLM3, HepG2, and Huh7, were used to evaluate the antitumor efficacy of HHT in vitro. Cytotoxicity and proliferative ability were evaluated by MTT and colony formation assays. Cell cycle progression and apoptosis in HHT-treated HCC cells were evaluated by flow cytometry. To determine the migration and invasion abilities of HCC cells, wound-healing and Transwell assays were used. Finally, western blot analysis was used to reveal the proteins involved. We also established a xenograft nude mouse model for in vivo assessments of the preclinical efficacy of HHT, mainly using hematoxylin and eosin staining, immunohistochemistry, ultrasound imaging (USI), and magnetic resonance imaging (MRI). HHT suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells, and induced cell cycle arrest at the G2 phase and apoptosis. In the HCC xenograft model, HHT showed an obvious tumor-suppressive effect. Surprisingly, Slug expression was also decreased by HHT via the PI3K/AKT/GSK3ß signaling pathway at least partially suppressed the growth of HCC via the PI3K/AKT/GSK3ß/Slug signaling pathway.

Three-Dimensional-Percolated Ceramic Nanoparticles along Natural-Cellulose-Derived Hierarchical Networks for High Li+ Conductivity and Mechanical Strength.

Solid polymer electrolytes for safe lithium batteries are in general flexible and easy to process, yet they have limited ionic conductivity and low mechanical strength. Introducing nano/microsized fillers into polymer electrolytes has been proven effective to address these issues, while formation of a percolated network of fillers for efficient Li+ conduction remains challenging. In this work, composite polymer electrolyte with 3D cellulose/ceramic networks is successfully developed using natural cellulose fibers and Li+-conducting ceramic nanoparticles. Monodisperse ceramic nanofillers first form interconnected networks driven by the self-assembly of hybrid cellulose fibers. The hierarchical cellulose skeleton provides spatial guidance for ceramic fillers and firmly supports the whole structure. After polymer electrolyte infusion, the resultant hybrid electrolyte affords both 3D continuous Li+ pathways for high Li+ conductivity and sufficient mechanical strength for dendrite suppression. This cellulose-confined particle percolation approach enables efficient and strong solid electrolytes for lithium batteries.

A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate.

Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis.

Efficient radiative transfer model for thermal infrared brightness temperature simulation in cloudy atmospheres.

An efficient radiative transfer model (ERTM) is developed to simulate thermal infrared brightness temperatures observed by the Advanced Himawari Imager (AHI) in this study. The ERTM contains an alternate mapping correlated k-distribution (AMCKD) scheme, a parameterization for cloud optical property, and a rapid infrared radiative transfer scheme. The AMCKD is employed to calculate the gaseous absorption in the inhomogeneous thermodynamic atmosphere. The optical properties of clouds are parameterized by the effective length for ice clouds based on the Voronoi model, and by the effective radius for water clouds based on the Lorenz-Mie theory. The adding method of four-stream discrete ordinates method (4DDA) is extended to be able to calculate the thermal infrared radiative intensity varying with the zenith angle in ERTM. The efficiency and accuracy of ERTM are evaluated by comparing with the benchmark model which is composed of discrete ordinate radiative transfer (DISORT) and line-by-line radiative transfer model (LBLRTM). Under the standard atmospheric profiles, the root mean square error (RMSE) of simulated brightness temperatures reaches a maximum of 0.21K at the B16 (13.28 µm) channel of AHI. The computational efficiency of ERTM is approximately five orders of magnitude higher than that of the benchmark model. Moreover, the simulated brightness temperatures by ERTM are highly consistent with the rigorous results and AHI observations in the application to the Typhoon Mujigae case.