Loss of Smek1 Induces Tauopathy and Triggers Neurodegeneration by Regulating Microtubule Stability.

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1-/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3ß (Gsk3ß) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner.

SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.

Obesity has become a major risk of global public health. SMEK1 is also known as a regulatory subunit of protein phosphatase 4 (PP4). Both PP4 and SMEK1 have been clarified in many metabolic functions, including the regulation of hepatic gluconeogenesis and glucose transporter gene expression in yeast. Whether SMEK1 participates in obesity and the broader metabolic role in mammals is unknown. Thus, we investigated the function of SMEK1 in white adipose tissue and glucose uptake. GWAS/GEPIA/GEO database was used to analyze the correlation between SMEK1 and metabolic phenotypes/lipid metabolism-related genes/obesity. Smek1 KO mice were generated to identify the role of SMEK1 in obesity and glucose homeostasis. Cell culture and differentiation of stromal-vascular fractions (SVFs) and 3T3-L1 were used to determine the mechanism. 2-NBDG was used to measure the glucose uptake. Compound C was used to confirm the role of AMPK. We elucidated that SMEK1 was correlated with obesity and adipogenesis. Smek1 deletion enhanced adipogenesis in both SVFs and 3T3-L1. Smek1 KO protected mice from obesity and had protective effects on metabolic disorders, including insulin resistance and inflammation. Smek1 KO mice had lower levels of fasting serum glucose. We found that SMEK1 ablation promoted glucose uptake by increasing p-AMPKα(T172) and the transcription of Glut4 when the effect on AMPK-regulated glucose uptake was due to the PP4 catalytic subunits (PPP4C). Our findings reveal a novel role of SMEK1 in obesity and glucose homeostasis, providing a potential new therapeutic target for obesity and metabolic dysfunction.NEW & NOTEWORTHY Our study clarified the relationship between SMEK1 and obesity for the first time and validated the conclusion in multiple ways by combining available data from public databases, human samples, and animal models. In addition, we clarified the role of SMEK1 in glucose uptake, providing an in-depth interpretation for the study of its function in glucose metabolism.

ECM1-associated miR-1260b promotes osteogenic differentiation by targeting GDI1.

Osteoporosis (OP) is a common disease among older adults. The promotion of osteoblast differentiation plays a crucial role in alleviating OP symptoms. Extracellular matrix protein 1 (ECM1) has been reported to be closely associated with osteogenic differentiation. In this study, we constructed U2OS cell lines with ECM1 knockdown and ECM1a overexpression based on knockdown, and identified the target miRNA (miR-1260b) by sequencing. Overexpression of miR-1260b promoted the osteogenic differentiation of U2OS and MG63 cells, as demonstrated by increased alkaline phosphatase (ALP) activity, matrix mineralization, and Runt-Related Transcription Factor 2 (RUNX2), Osteopontin (OPN), Collagen I (COL1A1), and Osteocalcin (OCN) protein expressions, whereas low expression of miR-1260b had the opposite effect. In addition, miR-1260b expression was decreased in OP patients than in non-OP patients. Next, we predicted the target gene of miRNA through TargetScan and miRDB and found that miR-1260b negatively regulated GDP dissociation inhibitor 1 (GDI1) by directly binding to its 3'-untranslated region. Subsequent experiments revealed that GDI1 overexpression decreased ALP activity and calcium deposit, reduced RUNX2, OPN, COL1A1, and OCN expression levels, and reversed the effects of miR-1260b on osteogenic differentiation. In conclusion, ECM1-related miR-1260b promotes osteogenic differentiation by targeting GDI1 in U2OS and MG63 cells. Thus, this study has significant implication for osteoporosis treatment.

Cadmium Absorption in Various Genotypes of Rice under Cadmium Stress.

Cadmium (Cd) is a kind of heavy metal. Cadmium pollution in paddy fields will accumulate a large amount of cadmium in rice, which will affect the growth and development of rice. In addition, long-term consumption of rice contaminated with Cd can harm human health. In this study, four rice varieties with high Cd accumulation (S4699, TLY619, JHY1586, QLY155) and four varieties with low Cd accumulation (YY4949, CYJ-7, G8YXSM, MXZ-2) were screened through field experiments for two consecutive years (2021 and 2022) and differences in antioxidant enzyme systems and expression of genes in their organs were analyzed. The total Cd content showed as follows: indica rice > japonica rice, high-Cd-accumulation variety > low-Cd-accumulation variety, and the total Cd content of each organ of rice showed root > stem > leaf > grain. The results of the antioxidant enzyme system showed that the contents of malondialdehyde (MAD), reduced glutathione (GSH), oxidized glutathione (GSSH), and peroxidase (POD) were positively correlated with the total Cd content in rice, and superoxide dismutase (SOD) showed the opposite performance in the leaves. There was no correlation between catalase (CAT) and Cd content, but CAT content decreased in leaves and grains and increased in roots and stems with increasing fertility. Based on this study, RT-qPCR was used to further validate the expression of Cd-uptake-related genes in different rice varieties. It was found that high expression of OsHMA3, OsCCX2, OsNRAMP5, and OsHMA9 genes promoted Cd uptake and translocation in rice, especially in rice varieties with high Cd accumulation. The high expression of OslRT1, OsPCR1, and OsMTP1 genes hindered Cd uptake by rice plants, which was especially evident in low-accumulating Cd rice varieties. These results provide an important theoretical reference and scientific basis for our in-depth study and understanding of the mechanism of cadmium stress tolerance in rice.

SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/ß-catenin signaling pathway.

PURPOSE: SMEK1, also known as PP4R3α, the regulatory subunit 3α of serine and threonine phosphatase PP4, participates in diversely critical biological processes such as the integration of centromere, deacetylation of histones, asymmetric divisions of neuroblast, and other crucial cellular activities. SMEK1 was formerly reported to play a part in carcinogenesis. This study aims to reveal the role of SMEK1 in lung adenocarcinoma and the underlying molecular mechanism. METHODS: Using immunohistochemical (IHC) staining, the protein level of SMEK1 in lung adenocarcinoma and adjacent non-tumor tissue was detected. The functional role of SMEK1 in cell proliferation and invasion was explored using cell counting kit-8 and Transwell assay, respectively. Xenograft tumor experiment was used to investigate the effect of SMEK1 on tumor growth in vivo. The alteration of Wnt/ß-catenin signaling pathway was detected by Western blotting, quantitative PCR, and dual-luciferase reporter assays. RESULTS: SMEK1 was highly expressed at the protein level in lung adenocarcinoma compared to the adjacent non-tumor tissue. In vitro, suppression of SMEK1 significantly decreased the proliferation, migration, and invasion of lung adenocarcinoma cell lines, while overexpression of SMEK1 enhanced above abilities. The xenograft model demonstrated that down-regulation of SMEK1 significantly inhibited tumor growth in vivo. In addition, we found that SMEK1 could positively regulate Wnt/ß-catenin signaling in lung adenocarcinoma cell lines. CONCLUSIONS: SMEK1 exerts a cancer-promoting effect in lung adenocarcinoma by activating Wnt/ß-catenin signaling.

Association of microRNA polymorphisms with gastric cancer risk in the North Chinese Han population.

Background and Aims: MicroRNA (miRNA) was found as a class of endogenous, important regulators of gene expression and involved in the regulation of many biological processes such as cell proliferation, apoptosis, and differentiation. Increasing studies have suggested that miR-146a, miR-196a2, and miR-499 play important roles in the development processes of gastric cancer (GC). The aim of our study is to investigate whether three common miRNA polymorphisms are associated with the susceptibility of GC. Materials and Methods: MiR-146a rs2910164 (G > C), miR-196a2 rs11614913 (C > T), and miR-499 rs3746444 (A > G) were genotyped by Taq-man assays in the present case-control study (386 patients, 341 controls). The associations between the selected miRNA single-nucleotide polymorphisms (SNPs) and the risk of GC were estimated by odds ratio (OR) with 95% confidence interval using logistic regression analysis. Results: Our results showed that none of the three SNPs was associated with the risk of GC in allelic frequencies and multiple genetic models. Further stratified analysis with regard to clinical-pathological parameters of GC patients indicated that miR-146a rs2910164 SNP was strongly associated with age (OR = 0.53, P = 0.001) and gender (OR = 0.61, P = 0.006). Conclusions: The present study showed no association of the investigated miRNA SNPs with the risk of GC in the north Chinese population.

Loss of BAF (mSWI/SNF) chromatin-remodeling ATPase Brg1 causes multiple malformations of cortical development in mice.

Mutations in genes encoding subunits of the BAF (BRG1/BRM-associated factor) complex cause various neurodevelopmental diseases. However, the underlying pathophysiology remains largely unknown. Here, we analyzed the function of Brahma-related gene 1 (Brg1), a core ATPase of BAF complexes, in the developing cerebral cortex. Loss of Brg1 causes several morphological defects resembling human malformations of cortical developments (MCDs), including microcephaly, cortical dysplasia, cobblestone lissencephaly and periventricular heterotopia. We demonstrated that neural progenitor cell renewal, neuronal differentiation, neuronal migration, apoptotic cell death, pial basement membrane and apical junctional complexes, which are associated with MCD formation, were impaired after Brg1 deletion. Furthermore, transcriptome profiling indicated that a large number of genes were deregulated. The deregulated genes were closely related to MCD formation, and most of these genes were bound by Brg1. Cumulatively, our study indicates an essential role of Brg1 in cortical development and provides a new possible pathogenesis underlying Brg1-based BAF complex-related neurodevelopmental disorders.

Ppp4r3a deficiency leads to depression-like behaviors in mice by modulating the synthesis of synaptic proteins.

Chronic stress is one of the main risk factors for the onset of major depressive disorder. Chronic unpredictable mild stress results in reduced expression of synaptic proteins and depression-like behaviors in rodent models. However, the upstream molecule that senses the demand for synaptic proteins and initiates their synthesis under chronic stress remains unknown. In this study, chronic unpredictable mild stress reduced the expression of PPP4R3A in the prefrontal cortex and hippocampus in mice. Selective knockout of Ppp4r3a in the cortex and hippocampus mimicked the depression- and anxiety-like behavioral effects of chronic stress in mice. Notably, Ppp4r3a deficiency led to downregulated mTORC1 signaling, which resulted in reduced synthesis of synaptic proteins and impaired synaptic functions. By contrast, overexpression of Ppp4r3a in the cortex and hippocampus protected against behavioral and synaptic deficits induced by chronic stress in a PPP4R3A-mTORC1-dependent manner. Rapamycin treatment of Ppp4r3a-overexpressing neurons blocked the regulatory effect of Ppp4r3a on the synthesis of synaptic proteins by directly inhibiting mTORC1. Overall, our results reveal a regulatory role of Ppp4r3a in driving synaptic protein synthesis in chronic stress.

Deficiency in WDFY4 reduces the number of CD8+ T cells via reactive oxygen species-induced apoptosis.

WDFY4 (WD repeat and FYVE domain-containing 4) is a susceptibility gene involved in several autoimmune diseases and plays an important role in the immune system. However, it is not clear how WDFY4 affects T cells. We have generated a Wdfy4-knockout mouse and found that selective deficiency of Wdfy4 in T cells led to a reduction in the number of CD8+ T cells in the periphery, thus promoting tumor growth when mice were challenged with a transplantable tumor. Moreover, conditional ablation of Wdfy4 in T cells enhanced the apoptosis of CD8+ T cells and increased the intracellular levels of reactive oxygen species accompanied by the upregulation of Nox2. Mechanistically, the decrease in the CD8+ T-cell numbers in Wdfy4-knockout mice was associated with activation of the p53 pathway and inhibition of the extracellular signal-regulated kinase pathway. In addition, WDFY4 participated in cell proliferation. In conclusion, our results elucidate the biological role of WDFY4 in apoptosis and establish a link between WDFY4 and T cells.

Lack of WDFY4 Aggravates Ovalbumin-Induced Asthma via Enhanced Th2 Cell Differentiation.

BACKGROUND: Asthma is a chronic inflammatory airway disease, and Th2 cells play an important role in asthma. WDFY4 (WDFY family member 4) is a susceptibility gene in several autoimmune diseases. OBJECTIVE: In this study, the roles of WDFY4 in Th2 cell differentiation and Th2-dependent asthma were investigated. METHODS: Naïve CD4+ T cells were isolated from wild-type and WDFY4-deficient mice and induced to differentiate in vitro. Subsequently, a mouse model of asthma was established by sensitization with ovalbumin. RESULTS: Study results showed that WDFY4 deficiency could promote the differentiation of Th2 cells and the production of Th2 cytokines. WDFY4-deficient asthmatic mice showed higher levels of Th2 cytokines in the lungs and bronchoalveolar lavage fluid than wild-type mice. Moreover, infiltration of inflammatory cells, hyperplasia of goblet cells, production of mucus, and deposition of collagen were enhanced in WDFY4-deficient asthmatic mice. CONCLUSIONS: Our study demonstrates the pivotal role of WDFY4 in the pathogenesis of asthma and in Th2 cell differentiation.

COL2A1 Mutation (c.611G>C) Leads to Early-Onset Osteoarthritis in a Chinese Family.

Mutations in the gene coding collagen type II α1 chain (COL2A1) are associated with a series of human disorders mainly involving the skeletal system. Here, we describe the second family with COL2A1 mutation, c.611G>C, Gly204Ala, leading to a replacement of glycine in the core triple helical (Gly-X-Y) domain of COL2A1 gene. The replacements of glycine in every third position of the triple with other amino acids will cause failure in the structure of type II collagen. The affected family members manifested early-onset osteoarthritis involving multiple joints. We propose that the COL2A1 gene should be taken into consideration for genetic counseling for patients with hereditary premature osteoarthritis and individuals carrying this mutation should receive early interventions for osteoarthritis.

Smek1 deficiency exacerbates experimental autoimmune encephalomyelitis by activating proinflammatory microglia and suppressing the IDO1-AhR pathway.

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal disease model of multiple sclerosis (MS) that involves the immune system and central nervous system (CNS). However, it is unclear how genetic predispositions promote neuroinflammation in MS and EAE. Here, we investigated how partial loss-of-function of suppressor of MEK1 (SMEK1), a regulatory subunit of protein phosphatase 4, facilitates the onset of MS and EAE. METHODS: C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish the EAE model. Clinical signs were recorded and pathogenesis was investigated after immunization. CNS tissues were analyzed by immunostaining, quantitative polymerase chain reaction (qPCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Single-cell analysis was carried out in the cortices and hippocampus. Splenic and lymph node cells were evaluated with flow cytometry, qPCR, and western blot analysis. RESULTS: Here, we showed that partial Smek1 deficiency caused more severe symptoms in the EAE model than in controls by activating myeloid cells and that Smek1 was required for maintaining immunosuppressive function by modulating the indoleamine 2,3-dioxygenase (IDO1)-aryl hydrocarbon receptor (AhR) pathway. Single-cell sequencing and an in vitro study showed that Smek1-deficient microglia and macrophages were preactivated at steady state. After MOG35-55 immunization, microglia and macrophages underwent hyperactivation and produced increased IL-1ß in Smek1-/+ mice at the peak stage. Moreover, dysfunction of the IDO1-AhR pathway resulted from the reduction of interferon γ (IFN-γ), enhanced antigen presentation ability, and inhibition of anti-inflammatory processes in Smek1-/+ EAE mice. CONCLUSIONS: The present study suggests a protective role of Smek1 in autoimmune demyelination pathogenesis via immune suppression and inflammation regulation in both the immune system and the central nervous system. Our findings provide an instructive basis for the roles of Smek1 in EAE and broaden the understanding of the genetic factors involved in the pathogenesis of autoimmune demyelination.

Berberine suppresses bladder cancer cell proliferation by inhibiting JAK1-STAT3 signaling via upregulation of miR-17-5p.

Hyperactivation of signal transducer and activator of transcription 3 (STAT3) is strongly associated with cancer initiation, progression, metastasis, chemoresistance, and immune evasion; thus, STAT3 has been intensely studied as a therapeutic target for cancer treatment. Berberine (BBR), an active component extracted from Coptis chinensis, has shown anti-tumor effects in multiple tumors. However, its underlying mechanisms have not yet been fully elucidated. In this study, we investigated the effects and the underlying mechanisms of BBR on bladder cancer (BCa) cells. We found that BBR showed significant cytotoxic effects against BCa cell lines both in vivo and in vitro, with much lower cytotoxic effects on the human normal urothelial cell line SV-HUC-1. BBR treatment induced DNA replication defects and cell cycle arrest, resulting in apoptosis or cell senescence, depending on p53 status, in BCa cells. Mechanistically, BBR exerted anti-tumor effects on BCa cells by inhibiting Janus kinase 1 (JAK1)-STAT3 signaling through the upregulation of miR-17-5p, which directly binds to the 3'UTR of JAK1 and STAT3, downregulating their expressions. Collectively, our results demonstrate that BBR exerts anti-tumor effects by perturbing JAK1-STAT3 signaling through the upregulation of miR-17-5p in BCa cells, and that BBR may serve as a potential therapeutic option for BCa treatment.

A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B and causes growth plate defects.

Endochondral ossification is the major process of long bone formation, and chondrogenesis is the final step of this process. Several studies have indicated that bone morphogenetic proteins (BMPs) are required for chondrogenesis and regulate multiple growth plate features. Abnormal BMP pathways lead to growth plate defects, resulting in osteochondrodysplasia. The SPARC-related modular calcium binding 2 (SMOC2) gene encodes an extracellular protein that is considered to be an antagonist of BMP signaling. In this study, we generated a mouse model by knocking-in the SMOC2 mutation (c.1076 T > G), which showed short-limbed dwarfism, reduced, disorganized, and hypocellular proliferative zones and expanded hypertrophic zones in tibial growth plates. To determine the underlying pathophysiological mechanism of SMOC2 mutation, we used knock-in mice to investigate the interaction between SMOC2 and the BMP-SMAD1/5/9 signaling pathway in vivo and in vitro. Eventually, we found that mutant SMOC2 could not bind to COL9A1 and HSPG. Furthermore, mutant SMOC2 inhibited BMP signaling by competitively binding to BMPR1B, which lead to defects in growth plates and short-limbed dwarfism in knock-in mice.

Correction to: A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus.

Figure 4a in Manuscript ID#JOCI-D-19-00318 has been revised due to the replacement of immunoblot lane of ß-catenin by Zo-1 in NHA group.

Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells.

BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration. METHODS: We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2'-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models. RESULTS: We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p. CONCLUSIONS: Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p.

A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus.

PURPOSE: Genome-wide association study of systemic lupus erythematosus (SLE) revealed tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) as a susceptibility gene. Here, we report a de novo mutation in TNFAIP3 in a Chinese patient with neuropsychiatric SLE (NPSLE). METHODS: Whole exome sequencing was performed for the patient and healthy members from the family. Suspected pathogenic variants were further analyzed and co-segregation was confirmed by Sanger sequencing. Real-time PCR and western blot were performed with peripheral blood mononuclear cells (PBMCs) and patient-derived T cells. Transfected HEK293T cells, human umbilical vein endothelial cells, normal human astrocytes, and microglia were used for in vitro studies. RESULTS: A de novo frameshift mutation in TNFAIP3 was found in the NPSLE patient. Western blot analysis showed activated NF-κB and mitogen-activated protein kinase pathways. Real-time PCR revealed elevated expression of pro-inflammatory cytokines. On immunoprecipitation assay, the mutant A20 altered the K63-linked ubiquitin level of TRAF6 via its ubiquitin-editing function. CONCLUSIONS: The mutant A20 may play a role in weakening the tight junction of the blood-brain barrier to cause neurologic symptoms. We report a rare variant of TNFAIP3 in a patient with NPSLE and reveal its autoimmune disease-causing mechanism in both peripheral tissues and the central nervous system.

Nongenetic optical modulation of neural stem cell proliferation and neuronal/glial differentiation.

Photostimulation has been widely used in neuromodulation. However, existing optogenetics techniques require genetic alternation of the targeted cell or tissue. Here, we report that neural stem cells (NSCs) constitutionally express blue/red light-sensitive photoreceptors. The proliferation and regulation of NSCs to neuronal or glial cells are wavelength-specific. Our results showed a 4.3-fold increase in proliferation and 2.7-fold increase in astrocyte differentiation for cells under low-power blue monochromatic light exposure (455 nm, 300 µW/cm2). The melanopsin (Opn4)/transient receptor potential channel 6 (TRPC6) non-visual opsin serves as a key photoreceptor response to blue light irradiation. Two-dimensional gel electrophoresis coupled with mass spectrometry further highlighted the Jun activation domain-binding protein 1 (Jab1) as a novel and specific modulator in phototransduction pathways induced by blue light exposure. Quiescent adult NSCs reside in specific regions of the mammalian brain. Therefore, we showed that melanopsin/TRPC6 expressed in these regions and blue light stimulation through optical fibers could directly stimulate the NSCs in vivo. Upconversion nanoparticles (UCNPs) converted deep-penetrating near-infrared (NIR) light into specific wavelengths of visible light. Accordingly, we demonstrated that UCNP-mediated NIR light could be used to modulate in vivo NSC differentiation in a less invasive manner. In the future, this light-triggered system of NSCs will enable nongenetic and noninvasive neuromodulation with therapeutic potential for central nervous system diseases.

Agronomic Management and Rice Varieties Controlling Cd Bioaccumulation in Rice.

Selection of rice varieties and application of amendments are effective measures to ensure food safety. Here we report that in the non-Cd area, the grain quality of all rice varieties met the Chinese National Grain Safety Standards (CNGSS). In the high-Cd area, rice varieties showed significant different bioaccumulation of Cd with lower rice yields than those in non-Cd area with the average decrease of 31.1%. There was a negative correlation between grain Cd content and yields. A total of 19 rice varieties were selected as low Cd accumulating rice varieties and their Cd content met CNGSS in the low-Cd area. Six of them met CNGSS in the high-Cd area. The application of amendments significantly reduced Cd content in rice grains by 1.0-84.7% with an average of 52.6% and 13 of varieties met CNGSS. The amendments reduced available Cd content in soils by 1.1-75.8% but had no significant effects on rice yields. Therefore, the current study implied that proper agronomic management with selection of rice varieties and soil amendments was essential in controlling Cd accumulation in rice grains.