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Biallelic mutations in POLR3A have been associated with childhood-onset hypomyelinating leukodystrophies and adolescent-to-adult-onset spastic ataxia, the latter of which has been linked to the intronic variant c.1909 + 22G>A. We report a case of adult-onset spastic ataxia in a 75-year-old man, being a compound heterozygous carrier of this variant, whose brain and spinal cord were for the first time investigated by neuropathological examination. We describe prominent degeneration of the posterior columns, spinocerebellar tracts, and anterior corticospinal tracts of the spinal cord in a pattern resembling Friedreich's ataxia, with a notable lack of significant white matter pathology throughout the brain, in marked contrast with childhood-onset cases. Immunohistochemical examination for the POLR3A protein demonstrated no apparent differences in localization or staining intensity between the proband and an age-matched control subject. We demonstrate the clinicopathologic description of POLR3A-related neurodegenerative disease and also mention the differential diagnosis of the childhood-onset hypomyelinating leukodystrophy and late-onset spastic ataxia phenotypes.

Spinocerebellar ataxia type 14 (SCA14) is a neurodegenerative disease caused by germline variants in the diacylglycerol (DAG)/Ca 2+ -regulated protein kinase Cγ (PKCγ), leading to Purkinje cell degeneration and progressive cerebellar dysfunction. Most of the identified mutations cluster in the DAG-sensing C1 domains. Here, we found with a FRET-based activity reporter that SCA14-associated PKCγ mutations, including a previously undescribed variant, D115Y, enhanced the basal activity of the kinase by compromising its autoinhibition. Unlike other mutations in PKC that impair its autoinhibition but lead to its degradation, the C1 domain mutations protected PKCγ from such down-regulation. This enhanced basal signaling rewired the brain phosphoproteome, as revealed by phosphoproteomic analysis of cerebella from mice expressing a human SCA14-associated H101Y mutant PKCγ transgene. Mutations that induced a high basal activity in vitro were associated with earlier average age of onset in patients. Furthermore, the extent of disrupted autoinhibition, but not agonist-stimulated activity, correlated with disease severity. Molecular modeling indicated that almost all SCA14 variants not within the C1 domain were located at interfaces with the C1B domain, suggesting that mutations in and proximal to the C1B domain are a susceptibility for SCA14 because they uniquely enhance PKCγ basal activity while protecting the enzyme from down-regulation. These results provide insight into how PKCγ activation is modulated and how deregulation of the cerebellar phosphoproteome by SCA14-associated mutations affects disease progression.

Objective Familial idiopathic basal ganglia calcification (FIBGC) is a rare, heritable disease characterized by calcium deposition in the basal ganglia and other brain regions. Clinical presentations are diverse, featuring an array of neurologic, psychiatric, and/or cognitive symptoms. This dyad report presents neurogenetic, neuroimaging, neurological, and serial neuropsychological data from a father (S1) and son (S2) with FIBGC. Method/Results The SLC20A2 genetic mutation c.1828-1831delTCCC was identified for each patient, both of whom evidenced similar patterns of brain calcification mainly in the basal ganglia and cerebellum on neuroimaging. S1’s onset was in his late 60s with primary motor abnormalities followed by cognitive decline; S2’s younger onset (late 30s) was characterized by predominant psychiatric symptoms and mild cognitive changes. Our unique, detailed longitudinal study revealed that both subjects demonstrated largely stable performance across most neuropsychological domains assessed. Conclusions The subjects’ differences in presentation demonstrate the variable expressivity in FIBGC even with the same pathogenic variant within a single family. Distinct phenotypes may be associated with age of onset even in persons with the same mutation, consistent with past research. Disease progression may feature an initial period of notable change from baseline followed by relative stability, as seen both on imaging and neuropsychological evaluation.

Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality.A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC).The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results.The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines.Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red.This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.

A novel sodium complex [Na2(L)2(Phen)2(H2O)2]·2(H2O) (L = 3-hydroxyquinoline-4-carboxylic acid anion; Phen = 1,10-phenanthroline) is synthesized by solvothermal approach and is structurally determined by single-crystal X-ray diffraction. The title complex crystallizes in the orthorhombic system of the Pbcn space group. The strong π⋯π stacking and hydrogen bonding interactions produce three-dimensional (3D) chains. A series of properties of the title complex were tested by solid-state photoluminescence, CIE analysis and solid-state diffuse reflectance. The results show that the title complex is a blue light emitter, CIE (x = 0.1542, y = 0.0211) and has an energy bandwidth of 1.607 eV. A novel sodium complex is synthesized via solvothermal approach, which is characteristic of an isolated structure. At the same time, it displays a narrow and intense photoluminescence emission band in the blue region and has an energy bandwidth of 1.607 eV.

Electromagnetic, external stimuli can be used to switch Metal-Organic Framework (MOF) materials and to achieve control over the pores of these materials on different ways. We designed MOFs with switchable moieties in their side-chains, such as azobenzene, to be switchable under irradiation of UV/Vis light. Additionally, we developed devices to be able to measure the impact of electromagnetic fields in-situ. We focused on surface anchored MOF (SURMOF) thin films, deposited on asymmetric, porous α-Al2O3 supports as gas separation membrane layers. It is possible to control the gas transport properties of the materials using, but also using electric fields, and measure changes gas separation (permeability and selectivity) of binary mixtures in-situ, using the Wicke-Kallenbach technique. The light switchable systems were investigated on their CO2 separation performance: By switching the azobenzene between cis and trans isomers inside the pore windows, it was possible to switch dipolar moments, thus changing the adsorption properties towards the quadrupolar moment of CO2. Using electric fields of 500 V/mm we could show on the prominent example of ZIF-8, a zeolitic imidazolate framework, that it has a strong impact on the gas transport properties, especially looking at the molecular sieving. The mechanistic of the electric field influence on the ZIF is as follows: The electric field distorts the lattice of the MOF, shifting the Zn2+ ions, lowering the symmetry of the unit cell. This effect leads to polarized polymophs of the structure, sharpening the molecular sieving through a stiffening effect. The purification of Propylene/Propane, a highly desired separation for the plastics industry, could be increased through the electric field stimuli by 33%. References Knebel, A. et al. Defibrillation of soft porous metal-organic frameworks with electric fields. Science 358, 347–351; 10.1126/science.aal2456 (2017). Wang, Z. et al. Tunable molecular separation by nanoporous membranes. Nat. Commun. 7, 13872; 10.1038/ncomms13872 (2016). Müller, K. et al. Switching Thin Films of Azobenzene-Containing Metal-Organic Frameworks with Visible Light. Chem. Eur. J. 23, 5434–5438; 10.1002/chem.201700989 (2017). Knebel, A. et al. Azobenzene Guest Molecules as Light-Switchable CO 2 Valves in an Ultrathin UiO-67 Membrane. Chem. Mater. 29, 3111–3117; 10.1021/acs.chemmater.7b00147 (2017). Tan, N. Y. et al. Investigation of the terahertz vibrational modes of ZIF-8 and ZIF-90 with terahertz time-domain spectroscopy. Chem Commun 51, 16037–16040; 10.1039/c5cc06455d (2015). Figure 1

Distal hereditary motor neuropathy (dHMN) is an inherited neuromuscular disease characterized by symmetric distal weakness and atrophy without sensory changes. There are about thirty known genes associated with dHMN, but together they explain only about a third of cases. Mutations in the sigma non-opioid intracellular receptor 1 gene (SIGMAR1) have been linked to autosomal recessive dHMN with pyramidal signs in several families. This phenotype can mimic amyotrophic lateral sclerosis (ALS). We report a 39-year-old man who was referred to our ALS clinic with distal motor weakness and hyperreflexia. Whole exome sequencing identified two novel variants in the SIGMAR1 gene in the proband. Targeted Sanger sequencing of asymptomatic family members confirmed that each carried one of these two variants. Our findings expand the number of known SIGMAR1 pathogenic variants associated with dHMN, which should be clinically distinguished from ALS.

Metal-organic frameworks (MOFs) are a class of crystalline porous coordination materials, which are assembled from inorganic nodes and organic linkers. Numerous applications, such as gas storage, molecule separation, catalysis, optical sensing, and charge transport, benefit from the outstanding properties of MOF materials. More advanced applications, e.g., in the electronics and optoelectronics area, demand homogeneous and monolithic MOF thin films. Recent studies demonstrated that surface-mounted MOFs (SURMOFs) are well suited to fulfill the requirements for the integration of MOFs into devices. As a crystalline thin-film material with tunable thickness, SURMOFs have been widely used in the optimization of chromophore stacking, electrical transport, stimuli-response, etc. The fabrication of SURMOFs is carried out employing a layer-by-layer (LbL) assembly technique, and it can yield MOF thin films with a well-defined orientation, tunable thickness, and editable crystalline heterostructure. We summarize the LbL assembly methods for SURMOF fabrication and the realization of advanced SURMOF architectures, including optical and electronic applications as well as the integration of photoactive SURMOFs and SURMOF-derived materials in technical devices. We conclude with a discussion of the challenges and prediction of the future of SURMOF materials.

For the first time, a procedure has been established for the growth of surface-anchored metal–organic framework (SURMOF) copper(II) benzene-1,4-dicarboxylate (Cu-BDC) thin films of thickness control with single molecule accuracy. For this, we exploit the novel method solution atomic layer deposition (sALD). The sALD growth rate has been determined at 4.5 Å per cycle. The compact and dense SURMOF films grown at room temperature by sALD possess a vastly superior film thickness uniformity than those deposited by conventional solution-based techniques, such as dipping and spraying while featuring clear crystallinity from 100 nm thickness. The highly controlled layer-by-layer growth mechanism of sALD proves crucial to prevent unwanted side reactions such as Ostwald ripening or detrimental island growth, ensuring continuous Cu-BDC film coverage. This successful demonstration of sALD-grown compact continuous Cu-BDC SURMOF films is a paradigm change and provides a key advancement enabling a multitude of applications that require continuous and ultrathin coatings while maintaining tight film thickness specifications, which were previously unattainable with conventional solution-based growth methods.

Elevated triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) are recognized as essential and independent hazard factors for total death and major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD). However, whether the increased TG/HDL-C forecasted the prognosis of CHD is still unknown. Therefore, we performed a meta-analysis to investigate the relationship between the elevated TG/HDL-C ratio and poor prognosis of CHD.A systematic literature search was conducted in PubMed, Web of Science, EMBASE, and The Cochrane Library, until August 30, 2021. Prospective observational studies regarding the association between TG/HDL-C and long-term mortality/MACEs in CHD patients were included.In total, 6 independent prospective studies of 10,222 participants with CHD were enrolled in the systematic and meta-analysis. Our outcomes of the meta-analysis indicated that the elevated TG/HDL-C group had a significantly increased risk of long-term all-cause mortality (hazard ratio [HR] = 2.92, 95% confidence interval [CI]: 1.75-4.86, P.05) and long-term MACEs (HR = 1.56, 95%CI 1.11-2.18, P.05).In patients with CHD, the present study showed that the high TG/HDL-C was associated with increased risk of long-term all-cause mortality and MACE.

Spinocerebellar ataxia type 14 (SCA14) is a neurodegenerative disease caused by germline variants in the diacylglycerol (DG)/Ca2+-regulated protein kinase C gamma (PKCγ), leading to Purkinje cell degeneration and progressive cerebellar dysfunction. The majority of the approximately 50 identified variants cluster to the DG-sensing C1 domains. Here, we use a FRET- based activity reporter to show that ataxia-associated PKCγ mutations enhance basal activity by compromising autoinhibition. Although impaired autoinhibition generally leads to PKC degradation, the C1 domain mutations protect PKCγ from phorbol ester-induced downregulation. Furthermore, it is the degree of disrupted autoinhibition, not changes in the amplitude of agonist- stimulated activity, that correlate with disease severity. This enhanced basal signaling rewires the brain phosphoproteome, as assessed by phosphoproteomic analysis of cerebella from mice expressing a human PKCγ transgene harboring a SCA14 C1 domain mutation, H101Y. Validating that the pathology arises from disrupted autoinhibition, we show that the degree of impaired autoinhibition correlates inversely with age of disease onset in patients: mutations that cause high basal activity are associated with early onset, whereas those that only modestly increase basal activity, including a previously undescribed variant, D115Y, are associated with later onset. Molecular modeling indicates that almost all SCA14 variants that are not in the C1 domains are at interfaces with the C1B domain, and bioinformatics analysis reveals that variants in the C1B domain are under-represented in cancer. Thus, clustering of SCA14 variants to the C1B domain provides a unique mechanism to enhance PKCγ basal activity while protecting the enzyme from downregulation, deregulating the cerebellar phosphoproteome.One Sentence SummarySCA14 driver mutations in PKCγ impair autoinhibition, with defect correlating inversely with age of disease onset.

International audience; High-yield wavelength conversion is one of the key requirements for efficient photon energy harvesting. Attempts to realize efficient conversion by simply stacking layers of chromophores have failed so far, even when using highly crystalline assemblies and employing the recently discovered long-range (>100 nm) Förster resonance energy transfer, LR-FRET. We were able to drastically improve optical conversion efficiency by using chromophoric metal-organic framework (MOF) heterolayers fabricated using layer-by-layer techniques in connection with an "antenna doping" strategy. Systematic investigations revealed that the LR-FRET mechanism, reported previously in chromophoric aggregates, is highly anisotropic for neat materials but can be made more isotropic by employing doping strategies. Using optimized fabrication parameters and dopant concentrations, a three-layer, two-step cascade with an overall optical conversion efficiency of ~ 75% has been realized.

We report herein seven novel lanthanide metal–organic frameworks (Ln-MOFs), [M(L27)(DMA)(H2O)·XH2O]n (TCZ-M), (M = Nd, Sm, Eu, Gd, Tb, Dy, Ho), (X = 2 or 3) (H3L27 = 2,7-bis(4-benzoic acid)-N-(4-benzoic acid)carbazole, DMA = N,N-dimethylacetamide, TCZ = “T”-shape carbazole-based MOFs, L27 = fully deprotonated H3L273− ligand). X-ray crystallography showed that all the TCZ-M (M = Nd, Sm, Eu, Gd, Tb, Dy, Ho) are isomorphous and possess a 3,6-connected three-dimensional (3D) framework with a point symbol of {4·62}2{42·610·83}. The photoluminescence measurement indicates that TCZ-Eu shows reddish-orange emission bands and TCZ-Sm shows both visible and near-infrared (NIR) emission bands. Magnetic susceptibility measurements show deviations from the Curie law mainly owing to the split of the ground term due to the ligand field and spin–orbit coupling in TCZ-Eu and TCZ-Sm. The magnetic properties of TCZ-M (M = Nd, Gd, Tb, Dy, Ho) are also investigated, and the results indicate a ferromagnetic interaction between the Tb3+ magnetic centers in TCZ-Tb and the antiferromagnetic interactions in TCZ-M (M = Nd, Gd, Dy, Ho).

Porous metal–organic frameworks (MOFs) with an extensive range of pore sizes have great potential for efficient separation of small organic molecules. Herein, we report a new stable porous metal–organic framework {Cu3L2(4,4′-BPD)[NH(CH3)2]·7DMA·12H2O}n (YCZ-1), which was fabricated from a Cu-paddlewheel metal node and a new linker, namely 3,6-bis(4-benzoic acid)-N-(4-benzoic acid) carbazole (H3L). YCZ-1 possesses a doubly interpenetrated 3,5,6-connected three-dimensional (3D) framework with a Schlafli symbol of {512·83}·{52·8}4·{56·84}2, which is a new topology. The crystalline size of YCZ-1 could be controlled by adding different doses of dimethylamine, which would also be generated from DMA dissociated during the solvothermal reaction. Meanwhile, with excellent structural stability and outstanding surface area, the crystalline material YCZ-1 could be utilized as a stationary phase for high performance liquid chromatography (HPLC) separations during the separation of small organic molecules.

The three-dimensional (3D) porous cobalt(II) metal-organic framework (MOF), [Co3(L)2(DMA)2(MeOH)2·4(DMA)·6(MeOH)]n (1) [L = fully deprotonated 2,7-bis(4-benzoic acid)-N-(4-benzoic acid) carbazole, DMA = N,N-dimethylacetamide], was synthesized by hydrothermal reaction. Based on X-ray single-crystal diffraction, structural analysis indicates that complex 1 crystallizes in the monoclinic C2/c space group. Complex 1 possesses a 3,6-connected three-dimensional (3D) topological structure with a point symbol of {42·6}2{44·62·87·102} when a trinuclear CoII cluster was regarded as 6-connected node and the organic ligands could be regarded as 3-connected linkers between the 6-connected nodes. The framework structure exhibits a one-dimension (1D) channel with an accessible void of 4223.0 A3, amounting to 42.8 % of the total unit-cell volume (9862.0 A3). Moreover, the magnetic properties of complex 1 were studied.

Lanthanide-based crystalline coatings have a great potential for energy-conversion devices, but until now luminescent surface-anchored materials were difficult to fabricate. Thin films, called lanthanides surface-mounted metal-organic frameworks (SURMOFs) with tetrasubstituted halide (fluorine, chlorine, and bromine) terephthalic acid derivative linkers as a basic platform for optical devices, exhibit a high quantum yield of fluorescence visible to the naked eyes under ambient light. We show that we can tune the luminescent properties in thin films by halide substitution, which affords control over the molecular structure of the material. We rationalize the mechanism for the modulation of the photophysical properties by "antenna effect", which controls the energy transfer and quantum yields using experimental and theoretical techniques for chelated lanthanides as a function of the type of atom substitutions at the phenyl rings and the resulting dihedral angle between phenyl rings in the linkers and carboxylate groups.

ObjectiveTo identify the genetic cause of autosomal dominant ataxia complicated by behavioral abnormalities, cognitive decline, and autism in 2 families and to characterize brain neuropathologic signatures of dominant STUB1-related ataxia and investigate the effects of pathogenic variants on STUB1 localization.MethodsClinical and research-based exome sequencing was used to identify the causative variants for autosomal dominant ataxia in 2 families. Gross and microscopic neuropathologic evaluations were performed on the brains of 4 affected individuals in these families.ResultsMutations in STUB1 have been primarily associated with childhood-onset autosomal recessive ataxia, but here we report heterozygous missense variants in STUB1 (p.Ile53Thr and p.The37Leu) confirming the recent reports of autosomal dominant inheritance. Cerebellar atrophy on imaging and cognitive deficits often preceded ataxia. Unique neuropathologic examination of the 4 brains showed the marked loss of Purkinje cells (PCs) without microscopic evidence of significant pathology outside the cerebellum. The normal pattern of polarized somatodendritic STUB1 protein expression in PCs was lost, resulting in aberrant STUB1 localization in the distal PC dendritic arbors.ConclusionsThis study confirms a dominant inheritance pattern in STUB1-ataxia in addition to a recessive one and documents its association with cognitive and behavioral disability, including autism. In the most extensive analysis of cerebellar pathology in this disease, we demonstrate disruption of STUB1 protein in PCs as part of the underlying pathogenesis.

Background Adenylate cyclase 5 (ADCY5)-related dyskinesia is a childhood-onset movement disorder. Manifestations vary in frequency and severity and may include chorea, tremor, dystonia, facial twitches, myoclonus, axial hypotonia, and limb hypertonia. Psychosis is likely part of the broader spectrum. ADCY5 is widely expressed in the brain, especially in the striatum. Previous reports of brain autopsies of 2 subjects with likely ADCY5-dyskinesia were limited by the absence of a molecular diagnosis. In 1 case, normal gross pathology was reported. In the other case, ADCY5 expression was not examined and neuropathological findings were confounded by age and comorbidities. Objectives To examine ADCY5 expression and neuropathological changes in ADCY5-dyskinesia. Methods An extensive brain autopsy, including immunohistochemical analyses with antibodies to paired helical filament tau, α-synuclein, amyloid-β, microtubule-associated protein 2, and ADCY5, was performed. Results The patient, with a p.M1029K ADCY5 variant, had severe dyskinesias from early childhood, later recurrent episodes of psychosis, and died at age 46. Gross pathology was unremarkable, but we detected increased immunoreactivity for ADCY5 in neurons in multiple brain regions. Despite no history of brain trauma to suggest chronic traumatic encephalopathy, we found tau deposits in the deep cortical sulci, midbrain, and hippocampus with minimal amyloid pathology and no Lewy bodies. Conclusions We present the first brain autopsy findings in a molecularly proven case of ADCY5-dyskinesia, showing increased ADCY5 immunoreactivity in neurons and evidence of tau deposition. Additional patients will need to be studied to determine whether increased immunoreactivity for ADCY5 is a signature for ADCY5-dyskinesia and whether this disease has a tauopathy component.

Three new binuclear cuprous complexes with similar tetraimine ligands [Cu2(pytzph)(POP)2](BF4)2 (1), [Cu2(pytzphcf)(POP)2](BF4)2 (2) and [Cu2(pytzphcz)(POP)2](BF4)2 (3), (pytzph = 6,6′-(1-phenyl-1,2,4-triazole-3,5-diyl)bis(2-methylpyridine), pytzphcf = 6,6′-(1-(4-(trifluoromethyl)phenyl)-1,2,4-triazole-3,5-diyl)bis(2-methylpyridine), pytzphcz = 9-(4-(3,5-bis(6-methylpyridin-2-yl)-1,2,4-triazol-1-yl)phenyl)-carbazole and POP = bis[2-(diphenylphosphine)phenyl]ether), have been synthesized and characterized in order to compare the different effects of substituent groups on the photoluminescence (PL) and electroluminescence (EL) properties. These complexes exhibit highly efficient green thermally activated delayed fluorescence (TADF) with short decay times (5.5–16 μs) and high photoluminescence quantum yields (up to 79%) at room temperature in the solid form. These complexes have essentially identical emission energy. However, the influence of the substituents on the photoluminescence and electroluminescence efficiencies is evident. Complex 3 with the carbazole group shows the highest efficiency in terms of both PL and EL, exhibiting an EQE of 8.3%, a CE of 27.1 cd A−1 and a peak brightness of 2525 cd cm−2 in the solution-processed OLED, while complex 2 with a trifluoromethyl appendage exhibits poorer quantum efficiency than the others.

Herein we report five porous luminescent coordination polymers (CPs), namely, [Zn3(L27)2(DMA)6(H2O)4]n (TCZ-001), [Zn3(L27)2(DMA)6(CH3CH2OH)2]n (TCZ-002), [Zn3(L27)2(DMA)6(CH3OH)]n (TCZ-003), [Cd3(L27)2(DMA)6(H2O)2]n (TCZ-004), and [Cd9(L27)6DMA13(4,4′-BPY)2(OH)2(H2O)13.5]n (TCZ-005) [H3L27 = 2,7-bis(4-benzoic acid)-N-(4-benzoic acid) carbazole, DMA = N,N-dimethylacetamide, 4,4′-BPY = 4,4′-bipyridine, TCZ = “T”-shape carbazole-based polymers, L27 = fully deprotonated H3L273− ligand]. All of the five CPs were assembled from a novel luminescent carbazole-based ligand. X-ray crystallography showed that TCZ-001 is a 3-connected one-dimensional (1D) chain structure with a {42·6} topology. TCZ-002 possesses a 3,6-connected three-dimensional (3D) framework with a point symbol of {42·6}2{44·62·87·102}. TCZ-003 displays a 3,6-connected two-dimensional 2D network with a Schlafli symbol of {411·64}·{43}2, which is a new topology. TCZ-004 features a 3,6-connected 2D net with a {43}2·{46·66·83} topology. In TCZ-005, the structure can be classified into two groups: one of the two groups is a 3-connected 1D chain structure with a {42·6} topology, similar to TCZ-001; the other one possesses a 3,3,3,4-connected network with a Schlafli symbol of {42·63·8}{42·6}3. The structure of TCZ-005 could be described as an SP 1-periodic net (4,4)(0,2) in the 1D_2D.ttd database. TCZ-001, TCZ-003 and TCZ-004 show a remarkable response to the Ni2+ concentration in DMA, H2O or EtOH. Some of Zn2+ ions were replaced by Ni2+ ions and the rate of the transmetalation depended on the concentration of Ni2+ ions. Also, changing part of the metal node would transform the colour of emitted light. Additionally, the colour of the luminescence displays a linear correlation with the Ni2+ concentration range from 0.005 to 0.35 M (mol L−1). Besides selective sensing of Ni2+, TCZ-004 can also be utilized to detect Eu3+ in DMA solution. Thus, several potential sensory probe materials for Ni2+ and Eu3+ detection in DMA solution have been obtained.

Metal organic frameworks (MOFs) are crystalline three-dimensional porous solids featuring a high surface area, which have attracted considerable attention in a wide range of applications e.g. in catalysis, hydrogen storage, gas separation, thermoelectric applications or as chemical sensors. Beyond solvothermal synthesis of bulk MOF crystals, growing MOFs thin films has been limited so far to rather conventional solution-based techniques. However, traditional growth methods from solution such as spin-coating, spray-coating or dip-coating generate MOFs thin films with a rather low film quality and an alarming lack of a precise film thickness control under 1 nm. This renders them unsuitable for most industrial applications and severely limits their future application potential. Atomic layer deposition (ALD) provides this capability, but is limited by the necessity to use gaseous precursors in vacuum conditions at temperatures typically above 100°C. This is incompatible with the typically high temperature sensitivity of many hybrid metal-organic compounds such as the MOFs. In this perspective, we have transferred the principles of ALD to precursors dissolved in liquid solvents. The ‘solution ALD’ (sALD) method can be implemented in a variety of microfluidic or slot-die processing devices. We have demonstrated that the principles of classical, gas-based ALD —self-limiting surface reactions— are reproduced in sALD. sALD shares the fundamental properties of standard ‘gas ALD’ (gALD), in particular the self-limiting surface chemistry and the ability to coat deep pores in a conformal manner Furthermore, sALD allows the experimentalist to design new, advantageous, reactions of known semiconductors (oxides, heavier chalcogenides), or to deposit materials otherwise inaccessible to ALD altogether, such as polymers, ionic solids, and metal-organic frameworks. They may be obtained in highly pure, crystalline form at room temperature, either as planar films or as conformal coatings of porous substrates. Based on these advances, we have been able to make the first sALD-derived films of a MOF, Cu-BDC. At any chosen thickness, sALD MOF films feature significantly lower roughness and better adhesion than those generated by the best spray-coating and dip-coating methods available currently.

By using a layer-by-layer (LbL) approach, we have fabricated lanthanide-based, monolithic metal-organic framework (MOF) thin films for optical applications. The thickness of the Ln-SURMOFs can be easily controlled, thereby maintaining its transparent properties, which makes them attractive for the field of optical coatings. Moreover, employing a hetero-epitaxy process, we demonstrated that Ln-SURMOF can be deposited on the top of other Ln-SURMOFs with different lanthanide ions, maintaining the crystallinity and orientation. The hetero-epitaxial multilayer architectures of Ln-SURMOF reduced the efficient energy transfer between different lanthanides ions and optimized the fabrication of Ln-MOF thin film with a straightforward modulation of the emission color. Meanwhile, the distance between lanthanide ions in Ln-SURMOFs was extended by replacing the linkers. These novel hetero-epitaxial Ln-SURMOF architectures, possess a bright future in the field of optics, photonics and optoelectronics.

Hundreds of genes have been implicated in autism spectrum disorders (ASDs). In genetically heterogeneous conditions, large families with multiple affected individuals provide strong evidence implicating a rare variant, and replication of the same variant in multiple families is unusual. We previously published linkage analyses and follow-up exome sequencing in seven large families with ASDs, implicating 14 rare exome variants. These included rs200195897, which was transmitted to four affected individuals in one family. We attempted replication of those variants in the MSSNG database. MSSNG is a unique resource for replication of ASD risk loci, containing whole genome sequence (WGS) on thousands of individuals diagnosed with ASDs and family members. For each exome variant, we obtained all carriers and their relatives in MSSNG, using a TDT test to quantify evidence for transmission and association. We replicated the transmission of rs200195897 to four affected individuals in three additional families. rs200195897 was also present in three singleton affected individuals, and no unaffected individuals other than transmitting parents. We identified two additional rare variants (rs566472488 and rs185038034) transmitted with rs200195897 on 1p36.33. Sanger sequencing confirmed the presence of these variants in the original family segregating rs200195897. To our knowledge, this is the first example of a rare haplotype being transmitted with ASD in multiple families. The candidate risk variants include a missense mutation in SAMD11, an intronic variant in NOC2L, and a regulatory region variant close to both genes. NOC2L is a transcription repressor, and several genes involved in transcription regulation have been previously associated with ASDs.

Objective: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 ( ADCY5 )–related dyskinesia and genotype–phenotype relationship. Methods: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases. Results: We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation. Conclusions: ADCY5 -related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis.

Lysophosphatidylserines (lyso-PSs) are a class of signaling lipids that regulate immunological and neurological processes. The metabolism of lyso-PSs remains poorly understood in vivo. Recently, we determined that ABHD12 is a major brain lyso-PS lipase, implicating lyso-PSs in the neurological disease polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC), which is caused by null mutations in the ABHD12 gene. Here, we couple activity-based profiling with pharmacological and genetic methods to annotate the poorly characterized enzyme ABHD16A as a phosphatidylserine (PS) lipase that generates lyso-PS in mammalian systems. We describe a small-molecule inhibitor of ABHD16A that depletes lyso-PSs from cells, including lymphoblasts derived from subjects with PHARC. In mouse macrophages, disruption of ABHD12 and ABHD16A respectively increases and decreases both lyso-PSs and lipopolysaccharide-induced cytokine production. Finally, Abhd16a(-/-) mice have decreased brain lyso-PSs, which runs counter to the elevation in lyso-PS in Abhd12(-/-) mice. Our findings illuminate an ABHD16A-ABHD12 axis that dynamically regulates lyso-PS metabolism in vivo, designating these enzymes as potential targets for treating neuroimmunological disorders.

Introduction Mutations in gap junction protein beta 1 (GJB1) on the X chromosome represent one of the most common causes of hereditary neuropathy. We assessed manifestations associated with a rare 3' untranslated region mutation (UTR) of GJB1 in a large family with X-linked Charcot-Marie-Tooth disease (CMTX). Methods Clinical, electrophysiological, and molecular genetic analyses were performed on an 8-generation family with CMTX. Results There were 22 affected males and 19 symptomatic females, including an 83-year-old woman followed for 40 years. Electrophysiological studies showed a primarily axonal neuropathy. The c.*15C>T mutation in the GJB1 3' UTR was identified in 4 branches of the family with a log of odds (LOD) of 4.91. This created a BstE II enzyme recognition site that enabled detection by restriction digestion. Discussion The c.*15C>T mutation in the GJB1 3' UTR segregates with CMTX1 in 8 generations. Penetrance in males and females is essentially complete. A straightforward genetic method to detect this mutation is described. Muscle Nerve 57: 859-862, 2018.

In this study, we investigated the effect of carbon nanotubes (CNTs) and performance of the prepared membranes. Thin film composite (TFC) forward osmosis (FO) membranes were fabricated based on the polyacrylonitrile (PAN) substrate, incorporating carbon nanotubes (CNTs) in the active skin layer. The CNTs can improve the water flux through added the hydrophilic groups. The mean surface roughness and hydrophilicity increased with the concentration of carbon nanotubes increased. The TFC membranes incorporated CNTs (0.2 wt%) exhibited the best FO performance with water flux of 25.14 L/m2·h and reverse salt flux of 8.64 g/m2·h using 0.5 M NaCl as draw solution and DI water as feed solution during FO test. The research provides us a promising approach to fabricate the high flux FO membranes.

Exome sequencing from a patient with neurological and developmental symptoms revealed two mutations in separate genes. One was a homozygous transition mutation that results in an in-frame, premature translational stop codon in the ZNF135 gene predicted to encode a transcriptional repressor. Another mutation was heterozygous, a single nucleotide duplication in the KCNN2 gene that encodes a Ca2+-activated K+ channel, SK2, and leads to a translational frame shift and a premature stop codon. Heterologous expression studies, brain slice recordings and coordination tests from a transgenic mouse line carrying the SK2 mutation suggest that it does not contribute to the patient’s symptoms. ZNF135 is expressed in human brain and it is likely that the homozygous mutation underlies the human phenotype.

Objective To identify the cause of childhood onset involuntary paroxysmal choreiform and dystonic movements in 2 unrelated sporadic cases and to investigate the functional effect of missense mutations in adenylyl cyclase 5 (ADCY5) in sporadic and inherited cases of autosomal dominant familial dyskinesia with facial myokymia (FDFM).

The structure of corn stubble was complex and closely combined with the soil, so dig location and root-soil separation are the urgent problem of the manufacturing of corn stubble harvesting machinery. This paper mainly focuses on investigating the interaction principles of corn stubble and soil which by the UU triaxial compression tests. Compared the shear strength of three different types of corn root-soil complexes (vertical root, horizontal root, complex root) and pure soil, and analyzed three important factors affecting the root-soil complex shear strength, it was shown that the presence of corn fibrous root can enhance the soil shear strength and different with their layout types. It will provide a theoretical basis for the design of bionic agricultural tillage components for root- soil separation.

This study is aiming at the practical problem of meat freshness evaluation. Since meat putrefaction is a complex process that is influenced by many factors, it is necessary to have a comprehensive investigation of the various indicators to determine the freshness of meat. This research integrated information from a multisensory system to reduce uncertainty of evaluation. According to the odor mechanism model of rotten chicken, six types of sensors were chosen, which were combined as array for olfactory experiments. WDW-20 electronic universal testing machine (UTM) was adopted as tactile sensing device. As a bionic tactile test part, the UTM head is to obtain pressure characteristic curves of the meat. According to the odor model and elastic mechanics parameters of the chicken, the mechanical parameters were analyzed under the condition of cold storage, as well as time-varying results of fingerprint odor signal and salt base nitrogen volatile signal. Then, established the meat odor, elastic mechanics and freshness parameters, which were integrated into a fusion system and combined with the data through the experimental test. Eventually, established the mathematical model among meat odor, elastic mechanics parameters and meat freshness. This study provides theory reference for the evaluation of meat freshness, and delivers new thought and method for the design of multiphase bionic intelligent electrical measuring equipment. (2014) Trans Tech Publications, Switzerland.

To detect the freshness of chicken quickly and accurately with non-destructive, in this paper, the gas-sensitive sensor array has been optimized according to the odor of chicken and the sensor experiment. gas sensors combinations of TGS2600 TGS2610 TGS2611 TGS2620 and TGS2442 were selected and combined to establish new sensor array,The outcome of biological olfactory research has been used to design a bionic gas collection chamber. We have also adopted RBF neural network as a pattern recognition method. The fact that the accuracy of chicken freshness detection using the system is physically and chemically proved to be 96% demonstrates the feasibility of making use of artificial olfactory system to detect chicken freshness.

Mole rat, a typical soil-burrowing animal, has high working efficiency during digging procedure, its claws are good biomimetic prototypes, and the geometrical structure of its claws and its movement type during digging can provide certain foundation for improving the design of the tillage implement. In this paper, based on the reverse engineering, the original data points of the claw was collected by a 3D laser scanner, then the accurate surface of the claw was created by using special software of reverse engineering on the premise of point-curve-surface method. The reconstructed CAD model was established in Pro/E software, and the model of interaction between the claws of mole rat and soil was obtained. The finite element method (FEM) was utilized to simulate the interaction of the claw against soil. The simulated results showed that the movement type of claw of mole rate during digging could get lower cutting resistance and bigger impact to soil.

Press roller is a commonly used tool for compacting soil to a suitable compactness. An ideal press roller should be able to ensure a low adhesion and rolling resistance in a suitable compaction. However, in tillage operation, the phenomenon of soil adhesion occurred widely when press roller worked. In this research, the ventral surface of dung beetles was taken as the bionic prototype and bionic ridged geometric structure press rollers were designed using ultra high molecular weight polyethylene material. Under the same testing conditions, press rollers with different geometrical details were conducted to examine the effect of ridge section diameter, ridge height to diameter ratio and the number of ridges along the circumference of the rollers on rolling resistance and soil adhesion. The results showed that the all bionic rollers exhibited lower adhesion than a conventional roller. While, only ridged bionic roller with suitable size could reduce rolling resistance. The bionic roller with the ridge diameter of 40 mm, dimensionless ratio of height to diameter of 0.5, the number of 12 indicated the lowest resistance in this work, 25 % lower than conventional roller.

The geometrical shapes of some animal organs have distinguished functions and properties that can provide useful information for bionic engineering applications. Hence, it is necessary to quantitatively measure the geometrical structure of those animal organs. However, some of the animal organs are tiny, complex and in the Meso-scale (0.1~10 mm). Their potential bionic application requires an accurate and efficient method to quantitatively analysis of their geometrical shapes. But existing methods are difficult and inefficient to quantitatively analysis. Yet, it was found that MATLAB image processing and computer vision technique can be advantageously exploited to obtain outer margin geometrical information from stereomicroscopy photograph. In this work, based on MATLAB, a program was designed and a method was proposed that specified for extract meso-scale animal organ outer margin contour points. The procedure for obtaining quantified geometrical information can be conclude as that stereomicroscope image of bionic object animal organ was prepared, the image to reduce noise interference was processed, the outer edge contour points was detected, and the points x and y coordinates data to computer database was stored. The foreleg of dung beetle Copris ochus Motschulsky, which is with special tooth-like structure for burrowing, the height of the end tooth is only around 1 mm and the width is about 0.5 mm, supported by this method, the outer edge profile of the foreleg end tooth was extracted from stereomicroscopy image with 669 × 727 pixels, about 1500 outer edge contour points was obtained, points x and y coordinates data were inputted to computer database for further analysis. This method is efficient, accurate and easy to adapt to quantitatively analysis of geometrical characteristic features of other animal organs in meso-scale.

The structure of corn stubble was complex and closely combined with the soil, so dig location and root-soil separation are the urgent problem of the manufacturing of corn stubble harvesting machinery. This paper mainly focuses on investigating the interaction principles of corn stubble and soil which by the UU triaxial compression tests. Compared the shear strength of three different types of corn root-soil complexes (vertical root, horizontal root, complex root) and pure soil, and analyzed three important factors affecting the root-soil complex shear strength, it was shown that the presence of corn fibrous root can enhance the soil shear strength and different with their layout types. It will provide a theoretical basis for the design of bionic agricultural tillage components for root- soil separation.

PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts) is a recently described autosomal-recessive neurodegenerative disease caused by mutations in the α-β-hydrolase domain-containing 12 gene (ABHD12). Only five homozygous ABHD12 mutations have been reported and the pathogenesis of PHARC remains unclear. We evaluated a woman who manifested short stature as well as the typical features of PHARC. Sequence analysis of ABHD12 revealed a novel heterozygous c.1129A>T (p.Lys377*) mutation. Targeted comparative genomic hybridization detected a 59-kb deletion that encompasses exon 1 of ABHD12 and exons 1-4 of an adjacent gene, GINS1, and includes the promoters of both genes. The heterozygous deletion was also carried by the patient's asymptomatic mother. Quantitative reverse transcription-PCR demonstrated ∼50% decreased expression of ABHD12 RNA in lymphoblastoid cell lines from both individuals. Activity-based protein profiling of serine hydrolases revealed absence of ABHD12 hydrolase activity in the patient and 50% reduction in her mother. This is the first report of compound heterozygosity in PHARC and the first study to describe how a mutation might affect ABHD12 expression and function. The possible involvement of haploinsufficiency for GINS1, a DNA replication complex protein, in the short stature of the patient and her mother requires further studies.

This paper investigates the impact of additives and cooling way on the metallization rate of reduction product by the experiment of the coal-based direct reduction of vanadium titanomagnetite ; The promotion of direct reduction product metallization by additive species, additive content, reduction time and cooling way was studied and the optimal condition was found; when used 3% CaF2 as additive reduced for 0.5h and used water quenching to cool down the product, finally got the product which metallization got 93.80% and 42.93% higher than the null sample.

The law of conservation of energy is an empirical law of physics. It states that the total amount of energy in an isolated system remains constant over time. And it is impossible to break. However, three of evidence presented in this paper cannot be explained by the Law of conservation of energy. Why is the magnetic potential energy gone when the magnet is antimatter annihilated? Why can the steady direct current (DC) be produced when coils are cutting magnetic lines without any obstruction? Why can’t the induced current hinder the change of temperature and magnetic flux? All of these just suggest that the total amount of energy in an isolated system is not conserved over time—the law of conservation of energy can be broken.

In this study, the dissipation of two antibiotics, sulfamethoxazole (SMX) and trimethoprim (TRM), in three soils under both aerobic and anaerobic conditions are evaluated. Under aerobic conditions, SMX dissipated rapidly through biodegradation but TRM was more persistent. Within the first 20 days in biologically active soils, >50% of the SMX was lost from the clay loam and loamy sand soils, and >80% loss was noted in the loam soil. Anaerobic dissipation of both compounds was more rapid than aerobic dissipation. The addition of manure to the soil only slightly increased the initial dissipation rate of the two compounds. Little effect was found on glucose mineralisation in soil following the addition of SMX and TRM, even as mixtures at high concentrations.

In the study, based on existing shells, clam shells for the study to focus on its combination of strength and deformation characteristics were investigated. Analysis of the microstructure on the mechanical properties of clam shells, aragonite sheet comparison between the critical load Lc1 and the prismatic layer of aragonite layer between the critical load Lc2 changes, discussed the critical load overall mechanical properties of materials influence. The results showed that, vertical clam shell when the growth surface can carry the load the maximum stress is mainly concentrated in about 55MPa. Along the growth direction of the load, the maximum stress range between 48.5MPa-61MPa, as opposed to vertical loading and stability. Compressed prismatic layer and nacreous layer of the maximum intensity was significantly higher than the overall compressive strength, maximum strength of layered compression is about 2 times the overall compressive strength, direction perpendicular to the surface when the load curve showed the characteristics of ceramics. Clam shell aragonite between the critical load for the chip 90N, prismatic layer and nacreous layer between the critical load of 120N. In this process, the emergence of brittle fracture characteristics of ceramics, and when the nacre is broken, there was even a class of metal material slippage.

In this paper，soil parameters and the collected data were tested and processed, and the changing trends of force with drilling depth were obtained and the maximum force applying to the working components was picked up. Compared with the smooth working component, the force applying to the unsmooth working components is smaller. Some parameters needed in Drucker-Prager soil model were measured and modified according to the basic tests. The simulation model was built in the finite element software -ANSYS. The simulation result is consistent with the actual testing result, which confirms the finite element model is correct .