Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

Identification and functional study of enhancers of EYA1, the causative gene of branchio-oto-renal syndrome.

INTRODUCTION: Branchio-oto-renal syndrome (BOR syndrome) is a rare genetic disorder with an incidence of 1 in 40,000, affecting the development of multiple organs, including the branchio, ear and kidney. It is responsible for 2% of childhood deafness. Currently, variants in the coding regions of the main causative genes, such as EYA1, SIX1, and SIX5, explain only half of the disease's etiology. Therefore, there is a need to explore the non-coding regions, which constitute the majority of the genome, especially the regulatory regions, as potential new causative factors. METHOD: In this study, we focused on the EYA1 gene, which accounts for over 40% of BOR syndrome cases, and conducted a screening of candidate enhancers within a 250 kb region upstream and downstream of the gene using comparative genomics. We characterized the enhancer activities of these candidates in zebrafish using the Tol2 transposon system. RESULTS: Our findings revealed that out of the 11 conserved non-coding elements (CNEs) examined, four exhibited enhancer activity. Notably, CNE16.39 and CNE16.45 displayed tissue-specific enhancer activity in the ear. CNE16.39required the full-length 206 bp sequence for inner-ear-specific expression, while the core functional region of CNE16.45 was identified as 136 bp. Confocal microscopy results demonstrated that both CNE16.39 and CNE16.45 drove the expression of GFP in the sensory region of the crista of the inner ear in zebrafish, consistent with the expression pattern of eya1. CONCLUSION: This study contributes to the understanding of the regulatory network governing EYA1 expression and offers new insights to further clarify the pathogenic role of EYA1 in BOR syndrome.

Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting.

The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 µA cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems.

Enhanced Photoelectrochemical Water Splitting of Black Silicon Photoanode with pH-Dependent Copper-Bipyridine Catalysts.

Since the water oxidation half-reaction requires the transfer of multi-electrons and the formation of O-O bond, it's crucial to investigate the catalytic behaviours of semiconductor photoanodes. In this work, a bio-inspired copper-bipyridine catalyst of Cu(dcbpy) is decorated on the nanoporous Si photoanode (black Si, b-Si). Under AM1.5G illumination, the b-Si/Cu(dcbpy) photoanode exhibits a high photocurrent density of 6.31 mA cm-2 at 1.5 VRHE at pH 11.0, which is dramatically improved from the b-Si photoanode (1.03 mA cm-2 ) and f-Si photoanode (0.0087 mA cm-2 ). Mechanism studies demonstrate that b-Si/Cu(dcbpy) has improved light-harvesting, interfacial charge-transfer, and surface area for water splitting. More interestingly, b-Si/Cu(dcbpy) exhibits a pH-dependent water oxidation behaviour with a minimum Tafel slope of 241 mV/dec and the lowest overpotential of 0.19 V at pH 11.0, which is due to the monomer/dimer equilibrium of copper catalyst. At pH ∼11, the formation of dimeric hydroxyl-complex could form O-O bond through a redox isomerization (RI) mechanism, which decreases the required potential for water oxidation. This in-depth understanding of pH-dependent water oxidation catalyst brings insights into the design of dimer water oxidation catalysts and efficient photoanodes for solar energy conversion.

Multifunctional Materials Serving as Efficient Non-Doped Violet-Blue Emitters and Host Materials for Phosphorescence.

Efficient multifunctional materials acting as violet-blue emitters, as well as host materials for phosphorescent OLEDs, are crucial but rare due to demand that they should have high first singlet state (S1 ) energy and first triplet state (T1 ) energy simultaneously. In this study, two new violet-blue bipolar fluorophores, TPA-PI-SBF and SBF-PI-SBF, were designed and synthesized by introducing the hole transporting moiety triphenylamine (TPA) and spirobifluorene (SBF) unit that has high T1 into high deep blue emission quantum yield group phenanthroimidazole (PI). As the results, the non-doped OLEDs based on TPA-PI-SBF exhibited excellent EL performance with a maximum external quantum efficiency (EQEmax ) of 6.76 % and a violet-blue emission with Commission Internationale de L'Eclairage (CIE) of (0.152, 0.059). The device based on SBF-PI-SBF displayed EQEmax of 6.19 % with CIE of (0.159, 0.049), which nearly matches the CIE coordinates of the violet-blue emitters standard of (0.131, 0.046). These EL performances are comparable to the best reported non-doped deep or violet-blue emissive OLEDs with CIEy<0.06 in recent years. Additionally, the green, yellow and red phosphorescent OLEDs with TPA-PI-SBF and SBF-PI-SBF as host materials achieved a high EQEmax of about 20 % and low efficiency roll-off at the ultra-high luminance of 10 000 cd m-2 . These results provided a new construction strategy for designing high-performance violet-blue emitters, as well as efficient host materials for phosphorescent OLEDs.

Spontaneous extracranial arterial dissections in a case of patient with osteogenesis imperfecta.

Background: Osteogenesis imperfecta (OI), also known as brittle bone disease, is an inherited disease characterized by increased bone brittleness and decreased bone mass. OI patients may also be associated with exoskeleton manifestations such as hearing loss, articular ligament laxity, and heart valve lesions. Reports of internal carotid and cerebral artery dissection related to OI patients are very rare. We present the first case of acute cerebral infarction caused by the progressive stripping of the carotid artery dissection Chinese patient with Osteogenesis imperfecta.Case: A 48-year-old Chinese male who had no prior medical history or bad habits was to admitted the hospital due to leftside temporal headache, paroxysmal right limb weakness, and prolonged blurred vision experienced for a week. After a series of tests were performed to exclude superficial temporal arteritis, the patient was diagnosed with transient ischemic attack and was given aspirin, clopidogrel and atorvastatin without further headache and blurred vision. However, he was again admitted to the emergency department the following day due to right limb weakness for 7 h that was considered acute cerebral infarction caused by left carotid artery dissection.Conclusion: The findings in this case support that internal carotid and cerebral artery dissection may be one of the complications of Osteogenesis imperfecta.

[Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways].

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 µg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated ß-galactosidase(SA-ß-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Identifying a Real Catalyst of [NiFe]-Hydrogenase Mimic for Exceptional H2 Photogeneration.

Inspired by the natural [NiFe]-H2 ase, we designed mimic 1, (dppe)Ni(µ-pdt)(µ-Cl)Ru(CO)2 Cl to realize effective H2 evolution under photocatalytic conditions. However, a new species 2 was captured in the course of photo-, electro-, and chemo- one-electron reduction. Experimental studies of in situ IR spectroscopy, EPR, NMR, X-ray absorption spectroscopy, and DFT calculations corroborated a dimeric structure of 2 as a closed-shell, symmetric structure with a RuI center. The isolated dimer 2 showed the real catalytic role in photocatalysis with a benchmark turnover frequency (TOF) of 1936 h-1 for H2 evolution, while mimic 1 worked as a pre-catalyst and evolved H2 only after being reduced to 2. The remarkably catalytic activity and unique dimer structure of 2 operated in photocatalysis unveiled a broad research prospect in hydrogenases mimics for advanced H2 evolution.

Hypericin-Loaded Carbon Nanohorn Hybrid for Combined Photodynamic and Photothermal Therapy in Vivo.

Photodynamic therapy (PDT) of hypericin (Hyp) is hampered by poor water solubility and photostability. Incorporation of photosensitizers into nanocarriers has been designed to solve these issues. Herein, SWNH-Hyps nanohybrids were first fabricated by loading hypericin on the surface of single-walled carbon nanohorns (SWNHs) through ??? interaction and exhibited high solubility and stability in aqueous water. SWNH-Hyps could be utilized for a single platform for cancer therapy because it could simultaneously generate enough reactive oxygen species and hyperthermia using light irradiation. Moreover, the SWNHs not only improved water solubility, photostability, and therapy effects of Hyp but also protected it from light degradation. SWNH-Hyps could effectively ablate 4T1 cells by photodynamic/photothermal synergistic therapy upon 590 and 808 nm light irradiations compared with PDT. Furthermore, remarkable tumor cell death as well as tumor growth inhibition was proved via photothermal therapy and PDT of SWNH-Hyps under 590 and 808 nm light irradiations, which demonstrated that synergistic anticancer ability of SWNH-Hyps was better than that of free Hyp in vivo. Such a simple and facile adsorption method improved water solubility of Hyp and then enhanced its therapy effect, which displays that SWNHs can be hopefully used in medicines in the future.

Altered behavioral responses to gamma-aminobutyric acid pharmacological agents in a mouse model of Huntington's disease.

BACKGROUND: Disruptions in gamma-aminobutyric (GABA) acid signaling are believed to be involved in Huntington's disease pathogenesis, but the regulation of GABAergic signaling remains elusive. Here we evaluated GABAergic signaling by examining the function of GABAergic drugs in Huntington's disease and the expression of GABAergic molecules using mouse models and human brain tissues from Huntington's disease. METHODS: We treated wild-type and R6/2 mice (a transgenic Huntington's disease mouse model) acutely with vehicle, diazepam, or gaboxadol (drugs that selectively target synaptic or extrasynaptic GABAA receptors) and monitored their locomotor activity. The expression levels of GABAA receptors and a major neuron-specific chloride extruder (potassium-chloride cotransporter-2) were analyzed by real-time quantitative polymerase chain reaction, Western blot, and immunocytochemistry. RESULTS: The R6/2 mice were less sensitive to the sedative effects of both drugs, suggesting reduced function of GABAA receptors. Consistently, the expression levels of α1/α2 and δ subunits were lower in the cortex and striatum of R6/2 mice. Similar results were also found in 2 other mouse models of Huntington's disease and in Huntington's disease patients. Moreover, the interaction and expression levels of potassium-chloride cotransporter-2 and its activator (brain-type creatine kinase) were decreased in Huntington's disease neurons. These findings collectively suggest impaired chloride homeostasis, which further dampens GABAA receptor-mediated inhibitory signaling in Huntington's disease brains. CONCLUSIONS: The dysregulated GABAergic responses and altered expression levels of GABAA receptors and potassium-chloride cotransporter-2 in Huntington's disease mice appear to be authentic and may contribute to the clinical manifestations of Huntington's disease patients. © 2017 International Parkinson and Movement Disorder Society.

Predictive efficacy of (11)C-PD153035 PET imaging for EGFR-tyrosine kinase inhibitor sensitivity in non-small cell lung cancer patients.

To determine the correlation of (11)C-PD153035 uptake with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity and phosphorylated EGFR (pEGFR) expression in non-small cell lung cancer (NSCLC) cell lines with different EGFR-TKI sensitivities and in their corresponding xenografts. Four human NSCLC cell lines (HCC827, PC9, A549, and H1975) in the logarithmic phase were co-incubated with (11)C-PD153035 to analyze the correlation of (11)C-PD153035 uptake with EGFR-TKI sensitivity, and EGFR/pEGFR expression. Nude mice xenograft models bearing the four NSCLCs were prepared. (11)C-PD153035 positron-emission tomography (PET)-computed tomography (CT) was used to image the xenografts and observe radioactive uptakes. Correlation of the in vivo uptakes with EGFR-TKI sensitivity, and EGFR/pEGFR expression was analyzed. HCC827 and PC9 cells, which were highly sensitive to EGFR-TKIs, exhibited higher (11)C-PD153035 uptakes than the other cells. A549 cells, which were moderately sensitive to EGFR-TKIs, showed higher uptake than the EGFR-TKI-resistant H1975 cells, which showed little or no uptake. Radioactive uptakes were positively correlated with pEGFR expression in all cells. PET-CT showed that radioactivity was highest in HCC827 xenografts. The radioactivity in PC9 xenografts was higher than that in A549 and H1975 xenografts. Tumor vs. non-tumor tissue ratio values were positively correlated with pEGFR expression in HCC827 and PC9 xenografts, but not in A549 and H1975 xenografts. In conclusion, (11)C-PD153035 can serve as an EGFR imaging agent in vitro and in vivo, and predicts sensitivity to EGFR-TKIs. This will provide an experimental basis for clinical applications of (11)C-PD153035 and individualized NSCLC therapy.

External Oxidant-Free Oxidative Cross-Coupling: A Photoredox Cobalt-Catalyzed Aromatic C-H Thiolation for Constructing C-S Bonds.

An external oxidant-free oxidative coupling for aromatic C-H thiolation by visible-light photoredox cobalt-catalysis has been developed. Various substrates could afford benzothiazoles in good to excellent yields, and only H2 is generated as a side product. When catalytic TBAOH was used as the base, not only 2-aryl but also 2-alkylbenzothiazoles could be obtained through this novel dehydrogenative coupling reaction. This method could be scaled up and applied to the synthesis of biologically active molecules bearing benzothiazole structural scaffolds (potent antitumor agents). Furthermore, the unexpected oxidation byproduct amides, which are often generated in oxidative cyclization of thiobenzanilides, can be completely avoided. Mechanistic studies showed that the H2 originates from the substrates. The kinetic studies indicate that the interaction between the cobalt catalyst and proton might be involved in the rate-limiting process.

Branched polyethylenimine improves hydrogen photoproduction from a CdSe quantum dot/[FeFe]-hydrogenase mimic system in neutral aqueous solutions.

Nature uses hydrogenase enzyme to catalyze proton reduction at pH 7 with overpotentials and catalytic efficiencies that rival platinum electrodes. Over the past several years, [FeFe]-hydrogenase ([FeFe]-H2 ase) mimics have been demonstrated to be effective catalysts for light-driven H2 evolution. However, it remains a significant challenge to realize H2 production by such an artificial photosynthetic system in neutral aqueous solution. Herein, we report a new system for photocatalytic H2 evolution working in a broad pH range, especially under neutral conditions. This unique system is consisted of branched polyethylenimine (PEI)-grafted [FeFe]-H2 ase mimic (PEI-g-Fe2 S2 ), MPA-CdSe quantum dots (MPA=mercaptopropionic acid), and ascorbic acid (H2 A) in water. Due to the secondary coordination sphere of PEI, which has high buffering capacity and stabilizing ability, the system is able to produce H2 under visible-light irradiation with turnover number of 10 600 based on the Fe2 S2 active site in PEI-g-Fe2 S2 . The stability and activity are much better than that of the same system under acidic or basic conditions and they are, to the best of our knowledge, the highest known to date for photocatalytic H2 evolution from a [FeFe]-H2 ase mimic in neutral aqueous solution.

Hepcidin1 knockout mice display defects in bone microarchitecture and changes of bone formation markers.

Iron accumulation is a risk factor of osteoporosis; mechanisms leading to iron-related bone loss are not fully determined. We sought to better understand the effect of chronic iron accumulation on bone over the life span in a mouse model. Hepcidin1 knockout (Hepc1(-/-)) male mice and their littermate control wild type (WT) mice at 7 months old were used in this study. Serum iron and ferritin as well as iron contents in liver and femur were significantly increased in Hepc1(-/-) mice compared to WT mice. We found that Hepc1(-/-) mice had a phenotype of low bone mass and alteration of the bone microarchitecture, most likely caused by a decreased osteoblastic activity. Cell culture studies indicated that chronic iron accumulation decreased bone formation, probably by affecting bone morphogenetic protein signaling.

Transplanted neural stem cells modulate regulatory T, γδ T cells and corresponding cytokines after intracerebral hemorrhage in rats.

The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Although studies have shown that transplanted neural stem cells (NSCs) protect the central nervous system (CNS) from inflammatory damage, their effects on subpopulations of T lymphocytes and their corresponding cytokines are largely unexplored. Here, rats were subjected to ICH and NSCs were intracerebrally injected at 3 h after ICH. The profiles of subpopulations of T cells in the brain and peripheral blood were analyzed by flow cytometry. We found that regulatory T (Treg) cells in the brain and peripheral blood were increased, but γδT cells (gamma delta T cells) were decreased, along with increased anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) and decreased pro-inflammatory cytokines (IL-6, and IFN-γ), compared to the vehicle-treated control. Our data suggest that transplanted NSCs protect brain injury after ICH via modulation of Treg and γδT cell infiltration and anti- and pro-inflammatory cytokine release.

Stepwise Toward Pure Blue Organic Light-Emitting Diodes by Synergetically Locking and Shielding Carbonyl/Nitrogen-Based MR-TADF Emitters.

Deep-blue multi-resonance (MR) emitters with stable and narrow full-width-at-half-maximum (FWHM) are of great importance for widening the color gamut of organic light-emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen-based MR core. Intramolecularly locking carbonyl/nitrogen-based bears narrower emission of 2,10-dimethyl-12,12-diphenyl-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione in solution and further with peripheral-shielding groups, deep-blue emitter (12,12-diphenyl-2,10-bis(9-phenyl-9H-fluoren-9-yl)-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione, DPQAO-F) exhibits ultra-pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO-F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper-device of DPQAO-F exhibits a record-high EQEmax of 32.7% in the deep-blue region, representing the first example of carbonyl/nitrogen-based OLED that can concurrently achieve narrow bandwidth in the deep-blue region and a high electroluminescent efficiency surpassing 30%.

Silicon photocathode functionalized with osmium complex catalyst for selective catalytic conversion of CO2 to methane.

Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s-1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching -14.11 mA cm-2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.

Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing.

BACKGROUND: Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application. AIM: To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs. METHODS: The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing. MSCs were pretreated with 5-pulse nsPEFs (100 ns at 10 kV/cm, 1 Hz), followed by total RNA isolation. Each transcript was normalized by fragments per kilobase per million. Fold change and difference significance were applied to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions, complemented by quantitative polymerase chain reaction verification. RESULTS: In total, 263 DEGs were discovered, with 92 upregulated and 171 downregulated. DEGs were predominantly enriched in epithelial cell proliferation, osteoblast differentiation, mesenchymal cell differentiation, nuclear division, and wound healing. Regarding cellular components, DEGs are primarily involved in condensed chromosome, chromosomal region, actin cytoskeleton, and kinetochore. From aspect of molecular functions, DEGs are mainly involved in glycosaminoglycan binding, integrin binding, nuclear steroid receptor activity, cytoskeletal motor activity, and steroid binding. Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation. CONCLUSION: Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs, 2 miRNAs, and 65 lncRNAs. Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways, which are involved in vesicular transport, calcium ion transport, cytoskeleton, and cell differentiation.

Galectin-3 aggravates microglial activation and tau transmission in tauopathy.

Alzheimer's disease is characterized by the accumulation of amyloid-ß plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a ß-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3-associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy.

[Magnetic resonance imaging study of effects of accommodation on human lens morphological characters].

OBJECTIVE: To evaluate the effects of accommodation on lens morphological characters. METHODS: From January 2011 to June 2011, magnetic resonance images of eyes were acquired from 30 subjects aged 20 to 24 years during accommodation and at rest. The optimal images were analyzed by Autocad 2010 to obtain the total lens cross-sectional area (CSA) and CSA of anterior and posterior portions of lens, anterior chamber depth, lens thickness, lens diameter, vitreous chamber depth and axial length during accommodation and at rest. Paired-t test was performed. RESULTS: The anterior curvature radius (mm), posterior curvature radius (mm), CSA of anterior portion (mm(2)), CSA of posterior portion (mm(2)), total lens CSA (mm(2)) was (8.7 ± 0.8), (6.2 ± 0.5), (7.5 ± 2.1), (12.0 ± 2.6), (20 ± 4) during relaxed accommodation; anterior curvature radius (mm), posterior curvature radius (mm), CSA of anterior portion (mm(2)), CSA of posterior portion (mm(2)), total lens CSA (mm(2)) was (7.1 ± 1.3), (5.6 ± 0.5), (14.7 ± 2.9), (12.2 ± 2.1) and (27 ± 4) during accommodation. The total lens CSA (t = -11.556, P < 0.01) and CSA of anterior portion (t = -15.653, P < 0.01) both increased in accommodative states. The CSA of posterior portion of lens (t = -0.437, P > 0.05) under a statistically independent accommodative state. There was significant difference in the anterior chamber depth (t = 4.366, P < 0.01), lens thickness (t = -5.456, P < 0.01) and lens diameter (t = 4.597, P < 0.01) in accommodative states. There were insignificant differences both in vitreous chamber depth (t = 0.428, P > 0.05) and axial length (t = 0.418, P > 0.05) under accommodative states. CONCLUSION: During accommodation, the anterior chamber depth decreases, lens thickness increases and diameter of lens decreases while anterior portions and total lens CSA increase. There are insignificant changes in posterior portions of lens CSA, vitreous chamber depth and axial length. The accommodative changes in CSA indicate that the anterior portion of lens may be related with the properties of anterior capsule and lens material, the position of zonular attachments and the location of fetal nucleus. Helmholtz theory is supported.