Hemizygous splicing variant in CNKSR2 results in X-linked intellectual developmental disorder.

BACKGROUND: Intellectual disability (ID) refers to a childhood-onset neurodevelopmental disorder with a prevalence of approximately 1%-3%. METHODS: We performed whole exome sequencing for the patient with ID. And the splicing variant we found was validated by minigene assay. RESULTS: Here, we report a boy with ID caused by a variant of CNKSR2. His neurological examination revealed hypsarrhythmia via electroencephalography and a right temporal polar arachnoid cyst via brain magnetic resonance imaging. A novel splicing variant in the CNKSR2 gene (NM_014927.5, c.1657+1G>A) was discovered by exome sequencing. The variant caused a 166 bp intron retention between exons 14 and 15, which was validated by a minigene assay. The variant was not reported in public databases such as gnomAD and the Exome Aggregation Consortium. CONCLUSIONS: The variant was predicted to be damaging to correct the translation of the CNKRS2 protein and was classified as likely pathogenic according to the ACMG guidelines.

Nonlinear spectral compression in high-power narrow-linewidth polarization maintaining fiber amplifiers for SBS suppression.

In this paper, we propose a method for narrowing the spectrum in high-power narrow-linewidth polarization-maintaining (PM) fiber amplifiers and investigate its potential for suppressing the stimulated Brillouin scattering (SBS). In this method, in addition to common phase modulation to suppress SBS, precisely designed amplitude modulation is induced to generate self-phase modulation in a high-power PM fiber amplifier. In this co-modulation way, the spectrum can be gradually compressed along the fiber. Compared to phase modulation alone or fiber-Bragg-gratings (FBGs) based narrow-linewidth fiber oscillator schemes, in which the spectrum remains the same or broadens, this scheme can achieve a higher SBS threshold for the same output spectral linewidth. Experiments on a ∼ 3 kW peak power quasi-continuous wave (QCW) fiber amplifier show that the co-modulation scheme can compress the spectrum from 0.25 nm to 0.084 nm as output peak power increases from 13 W to 3.2 kW and enhances the SBS threshold by ∼1.7 times compared to traditional FBGs-based fiber oscillator schemes, and by ∼1.4 times compared to common phase modulation schemes. This co-modulation scheme has the potential for mitigating SBS in high-power fiber amplifiers.

Generation of a human iPSC line (ZJSHDPi001-A) from peripheral blood mononuclear cells of a patient with Developmental epileptic encephalopathy-47 carrying FGF12 gene mutation (c.334G > A).

Developmental epileptic encephalopathy-47 (DEE47) is a nervous system disease characterized by the onset of intractable seizures that appear the first days or weeks after birth. FGF12 is the disease-causing gene of DEE47 that encodes a small cytoplasm protein, which is a member of the fibroblast growth factor homologous factor (FGF) family. The FGF12-encoded protein interacts with the cytoplasmic tail of voltage-gated sodium channels to enhance the voltage dependence of rapid inactivation of sodium channels in neurons. This study used non-insertion Sendai virus transfection to establish the induced pluripotent stem cells(iPSCs)line with FGF12 mutation. The cell line was obtained from a 3-year-old boy carrying the c.334G > A heterozygous mutation in the FGF12 gene. This iPSC line could facilitate the investigations of pathogeneses of complex nervous system diseases such as developmental epileptic encephalopathy.

Single-component hyaluronic acid hydrogel adhesive based on phenylboronic ester bonds for hemostasis and wound closure.

Hydrogel tissue adhesives that currently available are often fabricated by mixing two or more polymeric components. Single-component hydrogels afford injectability, strong and reversible adhesion remain a formidable challenge. This research describes the creation of the first single-component hyaluronic acid hydrogel adhesive-based on phenylboronic acid-diol ester linkages. Phenylboronic acid can not only serve as a cross-linker to form hydrogel, but also act as an adhesion site for glycosyl compounds found in biological cell membranes. The rheological and compressive tests for the hydrogel show that it has excellent self-healing properties, good injectability and strong compressive strength. Adhesion tests demonstrated that the hydrogel has significantly greater adhesion strength than commercial fibrin glue. These findings suggest that the rational design of hydrogel precursors facilitates the formation of single-component networks and multiple functionalities. In vivo studies further proved the hydrogel was an ideal bio-adhesive with biocompatibility, absorbed wound exudate and hemostasis, and accelerated wound closure.

A new technique for stain-marking of seeds with safranine to track seed dispersal and seed bank dynamics.

Accurate tracking of seed dispersal is critical for understanding gene flow and seed bank dynamics, and for predicting population distributions and spread. Available seed-tracking techniques are limited due to environmental and safety issues or requirements for expensive and specialized equipment. Furthermore, few techniques can be applied to studies of water-dispersed seeds. Here we introduce a new seed-tracking method using safranine to stain seeds/fruits by immersing in (ex situ) or spraying with (in situ) staining solution. The hue difference value between pre- and post-stained seeds/fruits was compared using the HSV color model to assess the effect of staining. A total of 181 kinds of seeds/fruits out of 233 tested species of farmland weeds, invasive alien herbaceous plants and trees could be effectively stained magenta to red in hue (320-360°) from generally yellowish appearance (30-70°), in which the other 39 ineffectively-stained species were distinguishable by the naked eye from pre-stained seeds. The most effectively stained seeds/fruits were those with fluffy pericarps, episperm, or appendages. Safranine staining was not found to affect seed weight or germination ability regardless of whether seeds were stained ex situ or in situ. For 44 of 48 buried species, the magenta color of stained seeds clearly remained recognizable for more than 5 months after seeds were buried in soil. Tracking experiments using four species (Beckmannia syzigachne, Oryza sativa f. spontanea, Solidago Canadensis, and Acer buergerianum), representing two noxious agricultural weeds, an alien invasive plant, and a tree, respectively, showed that the safranine staining technique can be widely applied for studying plant seed dispersal. Identifying and counting the stained seeds/fruits can be executed by specially complied Python-based program, based on OpenCV library for image processing and Numpy for data handling. From the above results, we conclude that staining with safranine is a cheap, reliable, easily recognized, automatically counted, persistent, environmentally safe, and user-friendly tracking-seed method. This technique may be widely applied to staining most of the seed plant species and the study of seed dispersal in arable land and in disturbed and natural terrestrial or hydrophytic ecological systems.

Gallium(III)-Mediated Dual-Cross-Linked Alginate Hydrogels with Antibacterial Properties for Promoting Infected Wound Healing.

The metal gallium has enormous promise in fighting infections by disrupting bacterial iron metabolism via a "Trojan horse" trick. It is well worth trying to study the potential of gallium-mediated hydrogel for treating infected wounds. Herein, on the basis of a conventional gelation strategy of sodium alginate combined with metal ions, Ga3+ has been innovatively given a dual role in a dual-cross-linked hydrogel. It acts nor only as a cross-linking agent to form a hydrogel material but also as a therapeutic agent to slow-release and continuously treat infected wounds. Further photo-cross-linking is introduced to improve the mechanical properties of the hydrogel. Thus, a new gallium ionic- and photo-dual-cross-linked alginate hydrogel, with broad-spectrum antimicrobial activity and strengthened mechanical performance, for the treatment of infected wounds is reported. The morphology, degradability, swelling behavior, rheological properties, and gallium release kinetics together indicated the homogeneous and the strengthened mechanical performance of this hydrogel but did not impede the release of gallium ions. Interestingly, in vitro and in vivo results also demonstrated its favorable biocompatibility, reduced bacterial growth, and accelerated infected wound healing, making the gallium-incorporated hydrogel an ideal antimicrobial dressing.

Fibroblast growth factor 21 improves lipopolysaccharide-induced pulmonary microvascular endothelial cell dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation.

Pneumonia is a common infectious disease of the respiratory system in children. It often leads to death in children by causing acute lung injury. Fibroblast growth factor 21 (FGF21) is a peptide hormone that plays an important role in the regulation of energy homeostasis. This study aimed to investigate the role of FGF21 in alleviating the lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMEC) injury, as well as the underlying mechanism. The expression of sirtuin 1 (SIRT1), NF-κB p65, Ac-NF-κB p65, apoptosis-related proteins, tight junction proteins and adhesion molecules in HPMECs were analyzed by Western blotting. The viability and apoptosis of HPMECs were detected by CCK-8 and TUNEL assays. Lactate dehydrogenase level and levels of inflammatory factors were respectively determined by assay kits. The mRNA expression of adhesion molecules in HPMECs was analyzed by RT-qPCR. As a result, SIRT1 expression was decreased and the expression of NF-κB p65 and Ac-NF-κB p65 were increased in LPS-induced HPMECs, which were reversed by recombinant FGF21 (rFGF21). rFGF21 increased the viability and inhibited the apoptosis, inflammatory response, permeability, and release of cell adhesion molecules of LPS-induced HPMECs. In addition, EX527 as SIRT1 inhibitor could reverse the effect of rFGF21 on LPS-induced HPMECs. In conclusion, FGF21 improved LPS-induced HPMEC dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation.

Microstructure determines floating ability of weed seeds.

BACKGROUND: Weed seeds in rice-wheat continuous cropping fields spread via flowing water during irrigation of the rice crop. However, the ability of their adaptation to water dispersal and their structural mechanisms remain unclear. One hundred and ten species of weed seeds from 35 families were selected for this study. Seed slices were made through freeze sectioning to observe and assess the proportions of parenchyma, aerenchyma and lignified tissue. Microstructure and morphological traits, such as relative size and appendages were integrated into an analysis. RESULTS: Multivariate statistical analysis showed that floating time was significantly positively correlated with the shape, aerenchyma and parenchyma of the weed seeds and negatively with lignified tissue. Cluster analysis divided all the tested seeds into four categories. The first category was super floating weeds, which had a large proportion of parenchyma or air chamber and floated on water surfaces for > 400 h, including 16 species; the second category was strong floating weeds, which had a flat shape, parenchyma or air chamber structures and floated for 120 to 400 h, including 17 species; the third category was floating weeds, which were usually dense in structure with a floating time < 120 h, including 78 species; the fourth category showed no floating ability with a large size and mass, and dense structures including seven species. CONCLUSION: Most weeds had floating ability, which was closely related to the adaptability of their anatomical structures. This study takes an insight into understanding ecological adaptation of weeds and the sustainable ecological weed control through removing floating weed seeds.