Genetic analysis of congenital unilateral renal agenesis in children based on next-generation sequencing.

BACKGROUND: Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear. METHODS: Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives. RESULTS: There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT). CONCLUSIONS: Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling. IMPACTS: We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.

Prognostic prediction of patients having classical papillary thyroid carcinoma with a 4 mRNA-based risk model.

The dysregulation of protein-coding genes involved in various biological functions is closely associated with the progression of thyroid cancer. This study aimed to investigate the effects of dysregulated gene expressions on the prognosis of classical papillary thyroid carcinoma (cPTC). Using expression profiling datasets from the Cancer Genome Atlas (TCGA) database, we performed differential expression analysis to identify differentially expressed genes (DEGs). Cox regression and Kaplan-Meier analysis were used to identify DEGs, which were used to construct a risk model to predict the prognosis of cPTC patients. Functional enrichment analysis unveiled the potential significance of co-expressed protein-encoding genes in tumors. We identified 4 DEGs (SALL3, PPBP, MYH1, and SYNDIG1), which were used to construct a risk model to predict the prognosis of cPTC patients. These 4 genes were independent of clinical parameters and could be functional in cPTC carcinogenesis. Furthermore, PPBP exhibited a strong correlation with poorer overall survival (OS) in the advanced stage of the disease. This study suggests that the 4-gene signature could be an independent prognostic biomarker to improve prognosis prediction in cPTC patients older than 46.

Development and evaluation of a family-child reading picture book on reducing autism spectrum disorder caregivers' psychological stress: a mixed method study.

Introduction: The rapid increasing prevalence of ASD has become a significant global health issue. Caregivers of children with ASD are experiencing higher level of psychological stress and mental disorders. However, interventions to improve the psychological health of caregivers of children with ASD have largely been neglected. Methods: Based on the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model, we initially did in-depth interviews with 8 caregivers, and conducted field observation in two rehabilitation centers to analyze the daily lives, the empowered components, the emotional moments of the children with autism and their caregivers. Then we designed the outline of the picture book, and developed it by a multi-disciplinary team by 4 rounds. After that, this picture book was sent out to 54 caregivers of children with ASD for family-child reading in one month. A quantitative questionnaire was administered before and after their reading to evaluate the efficacy of reducing their stress and affiliate stigma, and improving self-efficacy, resilience, empowerment capacity; and exit interviews were conducted after their initial reading to assess the acceptability, content appropriateness, perceived benefits and generalizability of this picture book. Quantitative data were analyzed by descriptive analysis and paired t-tests using IBM SPSS 26.0. Qualitative data were analyzed using template analysis. Results: In total, 54 caregivers read the picture book with their child, with the total of 149 (an average of 2.76 per family) times reading in one month. Among them, 39 caregivers returned the following-up questionnaires. Although most of the outcome measures did not showed significant changes except the stress level decreased statistically significant (13.38 ± 3.864 to 11.79 ± 3.238, P=0.001), caregivers reported that the picture book echoed their daily lives and gave them a sense of warmth, inspiration, and hope, as well as some insight on family relationships and attitudes towards the disorder. They also expressed a willingness to disseminate the book to other families with children suffering ASD and the public. Conclusion: This specially designed picture book has been proven to be an acceptable, content-appropriate, and effective family-centered psychological intervention, which could be easily scaled up.

Alginate nanogel-embedded liposomal drug carriers facilitate drug delivery efficiency in arthritis treatment.

Despite numerous advantages of liposomes in treating rheumatoid arthritis (RA), the in vivo stability remains a critical issue. Current strategies for improving liposomal stability often compromise their original properties. Herein, we designed an alginate nanogel-embedded liposome aiming at retaining those inherent advantages while enhancing their in vivo stability. The introduction of alginate network within the liposome core can provide mechanical support and controlled drug release without affecting the surface properties. Results showed the cross-linking of alginate network within the inner core of liposomes elevated the particle rigidity to 3 times, allowing for improved stability and decreased drug leakage. Moreover, this nanogel-embedded liposome with optimized elasticity obviously facilitated cellular uptake in inflammatory macrophages. When entering blood circulation, increased rigidity altered the composition of protein corona on the particle surface, resulting in 2-fold increase in circulation time and improved drug accumulation in arthritic joints. When anti-inflammatory chlorogenic acid (CA) was encapsulated into the nanogel network, this CA-loaded nanogel-embedded liposome significantly inhibited ROS production and inflammatory response, ultimately achieved superior therapeutic outcome in arthritic rats. Results demonstrated that this nanogel-embedded liposomes can essentially retain the inherent advantages and overcome the drawbacks of liposomes, thereby improving the drug delivery efficiency.

A high internal heat flux and large core in a warm neptune exoplanet.

Interactions between exoplanetary atmospheres and internal properties have long been hypothesized to be drivers of the inflation mechanisms of gaseous planets and apparent atmospheric chemical disequilibrium conditions1. However, transmission spectra of exoplanets has been limited in its ability to observational confirm these theories due to the limited wavelength coverage of HST and inferences of single molecules, mostly H2O (ref. 2). In this work, we present the panchromatic transmission spectrum of the approximately 750 K, low-density, Neptune-sized exoplanet WASP-107b using a combination of HST WFC3, JWST NIRCam and MIRI. From this spectrum, we detect spectroscopic features due to H2O (21σ), CH4 (5σ), CO (7σ), CO2 (29σ), SO2 (9σ), and NH3 (6σ). The presence of these molecules enable constraints on the atmospheric metal enrichment (M/H is 10-18× Solar3), vertical mixing strength (log10Kzz = 8.4-9.0 cm2s-1), and internal temperature (>345 K). The high internal temperature is suggestive of tidally-driven inflation4 acting upon a Neptunelike internal structure, which can naturally explain the planet's large radius and low density. These findings suggest that eccentricity driven tidal heating is a critical process governing atmospheric chemistry and interior structure inferences for a majority of the cool (<1,000K) super-Earth-to-Saturn mass exoplanet population.

C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.

The dual-configured hydrogen bonds induced by polymerized deep eutectic solvents-modified magnetic biochar enhanced the selectivity for 3,4-methylenedioxymethamphetamine.

The accurate discovering and monitoring of 3,4-methylenedioxymethamphetamine (MDMA) are especially important because of its substantial toxicity and potential harm to human and the ecological systems. Three types of polymerized deep eutectic solvents functionalized magnetic biochar (MBC@poly (AA/AAC/AAm-ChCl)) were successfully synthesized to adsorb MDMA. The isotherm and kinetic data confirmed that MBC@poly (AAm-ChCl) had the strongest adsorption capacity, and the order of adsorption capacity is as follow: MBC@poly(AAm-ChCl) > MBC@poly(AA-ChCl) > MBC@poly(MAA-ChCl), which also revealed that the adsorption was heterogeneous multi-layer chemisorption. The findings of the characterizations manifested that MBC@poly(AAm-ChCl) was the optimal adsorbent owning to its higher nitrogen content, resulting in the formation of a greater number of hydrogen bonds. Due to the strong hydrogen bonding effect of CO and -NH2 functional groups, MBC@poly(AAm-ChCl) exhibited the high selectivity towards MDMA under the coexistence of multiple chemical substances, and excellent adsorption performance over the pH range of 4-11. Urea as a hydrogen bond inhibitor further confirmed MBC@poly(AAm-ChCl) had high-density active hydrogen bonding sites. Furthermore, utilizing density functional theory (DFT) for simulating adsorption both before and after the process verified that the high selectivity of MBC@poly(AAm-ChCl) attributed to the formation of the dual-configured hydrogen bonds. This study provides support for the production of highly selective biochar for use in pretreatment during drug detection.

Establishment of an induced pluripotent stem cell (iPSC) line (INNDSUi004-A) from a patient with Congenital Nemaline Myopathy.

We used a non-integrated reprogramming approach to establish a human induced pluripotent stem cell (hiPSC) line (INNDSUi004-A) from the skin fibroblasts of a 13-year-old female individual with Congenital Nemaline Myopath. The cells obtained have typical characteristics of embryonic stem cells, show expression of specific pluripotency markers, and can differentiate into three germ layers in vitro. This iPSC cell line has the genetic information of the patient and is a good model for studying disease mechanisms and developing novel therapies.

TMX2 potentiates cell viability of hepatocellular carcinoma by promoting autophagy and mitophagy.

The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment.Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.

AMPK regulates immature boar Sertoli cell proliferation through affecting CDK4/Cyclin D3 pathway and mitochondrial function.

Sertoli cell (SC) proliferation plays an important role in sperm production and quality; however, the regulatory mechanism of SC proliferation is not well understood. This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of immature boar SC activity. Cell counting kit-8, Seahorse XFe96, mitochondrial respiratory enzyme-related assay kits, and transmission electron microscopy were used to detect SC proliferative viability, oxygen consumption rate (OCR), mitochondrial respiratory enzyme activity, and the ultrastructure of primary cultured SCs in vitro from the testes of 21-day-old boars. A dual luciferase reporter assay was performed to determine the miRNA-mRNA target interaction. Western blotting was used to analyze cell proliferation-related protein expression of p38, p21, proliferating cell nuclear antigen (PCNA), Cyclin-dependent kinase 4 (CDK4), Cyclin D3, and phosphorylated retinoblastoma protein (Rb). Each experiment had a completely randomized design, with three replicates in each experiment. The results showed that the AMPK inhibitor (Compound C, 20 µM-24 h) increased cell proliferation viability, ATP production, and maximal respiration of SCs by 0.64-, 0.12-, and 0.08-fold (p < 0.05), respectively; increased the SC protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.13-, 0.09-, 0.88-, and 0.12-fold (p < 0.05), respectively; and decreased the SC protein expression of p38 and p21 by 0.36- and 0.27-fold (p < 0.05), respectively. The AMPK agonist AICAR (2 mM-6 h) significantly inhibited SC ultrastructure, OCR, mitochondrial respiratory enzyme activity, and cell proliferation-related protein levels. AMPK was validated to be a target gene of miR-1285 based on the result in which the miR-1285 mimic inhibited the luciferase activity of wild-type AMPK by 0.54-fold (p < 0.001). MiR-1285 mimic promoted the OCR of SCs, with 0.45-, 0.15-, 0.21-, and 0.30-fold (p < 0.01) increases in ATP production, basal and maximal respiration, and spare capacity, respectively. MiR-1285 mimic increased the mitochondrial respiratory enzyme activity of SCs, with 0.63-, 0.70-, and 0.97-fold (p < 0.01) increases in NADH-Q oxidoreductase, cytochrome c oxidase, and ATP synthase, respectively. Moreover, the miR-1285 mimic increased the protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.24-, 0.30-, 0.22-, and 0.13-fold (p < 0.05), respectively, and reduced the protein expression of p38 and p21 by 0.58- and 0.66-fold (p < 0.001). MiR-1285 inhibitor showed opposite effects on the above indicators and induced numerous autophagosomes and large lipid droplets in SCs. A high dose of estradiol (10 µM-6 h, showed a promotion of AMPK activation in a previous study) significantly inhibited SC ultrastructure, mitochondrial function, and proliferation-related pathways, while these adverse effects were weakened by Compound C treatment or miR-1285 mimic transfection. Our findings suggest that the activation and inhibition of AMPK induced by specific drugs or synthesized targeted miRNA fragments could regulate immature boar SC proliferative activity by influencing the CDK4/Cyclin D3 pathway and mitochondrial function; this helps to provide a basis for the prevention and treatment of male sterility in clinical practice.

DNA methylation plays important roles in lifestyle transition of Arthrobotrys oligospora.

Trap formation is the key indicator of carnivorous lifestyle transition of nematode-trapping fungi (NTF). Here, the DNA methylation profile was explored during trap induction of Arthrobotrys oligospora, a typical NTF that captures nematodes by developing adhesive networks. Whole-genome bisulfite sequencing identified 871 methylation sites and 1979 differentially methylated regions (DMRs). This first-of-its-kind investigation unveiled the widespread presence of methylation systems in NTF, and suggested potential regulation of ribosomal RNAs through DNA methylation. Functional analysis indicated DNA methylation's involvement in complex gene regulations during trap induction, impacting multiple biological processes like response to stimulus, transporter activity, cell reproduction and molecular function regulator. These findings provide a glimpse into the important roles of DNA methylation in trap induction and offer new insights for understanding the molecular mechanisms driving carnivorous lifestyle transition of NTF.

Overcoming strength-ductility tradeoff with high pressure thermal treatment.

Conventional material processing approaches often achieve strengthening of materials at the cost of reduced ductility. Here, we show that high-pressure and high-temperature (HPHT) treatment can help overcome the strength-ductility trade-off in structural materials. We report an initially strong-yet-brittle eutectic high entropy alloy simultaneously doubling its strength to 1150 MPa and its tensile ductility to 36% after the HPHT treatment. Such strength-ductility synergy is attributed to the HPHT-induced formation of a hierarchically patterned microstructure with coherent interfaces, which promotes multiple deformation mechanisms, including dislocations, stacking faults, microbands and deformation twins, at multiple length scales. More importantly, the HPHT-induced microstructure helps relieve stress concentration at the interfaces, thereby arresting interfacial cracking commonly observed in traditional eutectic high entropy alloys. These findings suggest a new direction of research in employing HPHT techniques to help develop next generation structural materials.

Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

Big data empowerment: Digital transformation and governance of minority shareholders: Evidence from China.

Based on the analysis of data from listed enterprises in China between 2011 and 2022, we investigate the influence of digital transformation on the governance efficiency for minority shareholders. The results show that the extent of digital transformation exert a negative effect on the agency costs incurred from related-party transactions. The mechanism examination elucidates that digital transformation augments the governance efficiency for minority shareholders by boosting attendance at shareholders' meetings and enhancing the exit threat for minority shareholders. Subsequent analysis reveals that non-state-owned enterprises, compared to state-owned enterprises, exhibit a more pronounced effect in diminishing the second type of agency costs through digital transformation. Furthermore, the impact of digital transformation in curtailing agency costs is more significant in the eastern regions than central and western regions. The better the equity checks and balances in listed enterprises, the more effective digital transformation is in reducing agency costs. This study offers valuable insights for bolstering the governance capacity of minority shareholders in the context of digital transformation.

ENO1 promotes trophoblast invasion regulated by E2F8 in recurrent miscarriage.

Recurrent miscarriage (RM) is related to the dysfunction of extravillous trophoblast cells (EVTs), but the comprehensive mechanisms remain largely unexplored. We analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing and microarray datasets obtained from Gene Expression Omnibus (GEO) database to explore the hub genes in the mechanisms of RM. We identified 1724 differentially expressed genes (DEGs) in EVTs from the RM, and they were all expressed along the trajectory of EVTs. These DEGs were associated with hypoxia and glucose metabolism. Single-cell Regulatory Network Inference and Clustering (SCENIC) analysis revealed that E2F transcription factor (E2F) 8 (E2F8) was a key transcription factor for these DEGs. And the expression of ENO1 can be positively regulated by E2F8 via RNA sequencing analysis. Subsequently, we performed immunofluorescence assay (IF), plasmid transfection, western blotting, chromatin immunoprecipitation (ChIP), real-time quantitative polymerase chain reaction (qRT-PCR), and transwell assays for validation experiments. We found that the expression of alpha-Enolase 1 (ENO1) was lower in the placentas of RM. Importantly, E2F8 can transcriptionally regulate the expression of ENO1 to promote the invasion of trophoblast cells by inhibiting secreted frizzled-related protein 1/4 (SFRP1/4) to activate Wnt signaling pathway. Our results suggest that ENO1 can promote trophoblast invasion via an E2F8-dependent manner, highlighting a potential novel target for the physiological mechanisms of RM.

Efficient magnetic solid-phase extraction, UPLC-MS/MS detection, and consumption assessment of five trace psychoactive substances.

Wastewater-based epidemiology (WBE) has become an objective and updated surveillance strategy for monitoring and estimating consumption trends of psychoactive substances (PSs) in the population. Firstly, magnetic shrimp shell biochar-based adsorbent (DZMBC) was synthesized and employed for extraction trace PSs from municipal wastewater. Proper pyrolysis temperature and increased KOH activator content favored the pore structure and surface area, thus facilitating extraction. DZMBC delivered exceptional extraction performance such as pH stability, anti-interference property, fast magnetic separation ability, reusability, and reproducibility. Then, a method based on magnetic solid-phase extraction (MSPE) followed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed, validated, and utilized for the quantitative determination of five PSs in real wastewater samples. Methodological validation results indicated a favorable linearity, low method limits of detection (1.00-4.75 ng/L), and good precisions (intra-day and inter-day relative standard deviations < 4.8%). Finally, an objective snapshot of Chongqing drug use and consumption pattern was obtained. Methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA) were the prevalent illegal drugs in local. Both concentrations and per capita consumption of MDMA displayed a change (P < 0.05) between July and September, while no statistical differences were observed for each week.

Peroxydisulfate-Driven Reductive Dechlorination as Affected by Soil Constituents: Free Radical Formation and Conversion.

We report a previously unrecognized but efficient reductive degradation pathway in peroxydisulfate (PDS)-driven soil remediation. With supplements of naturally occurring low-molecular-weight organic acids (LMWOAs) in anaerobic biochar-activated PDS systems, degradation rates of 12 γ-hexachlorocyclohexanes (HCH)-spiked soils boosted from 40% without LMWOAs to a maximum of 99% with 1 mM malic acid. Structural analysis revealed that an increase in α-hydroxyl groups and a diminution in pKa1 values of LMWOAs facilitated the formation of reductive carboxyl anion radicals (COO•-) via electrophilic attack by SO4•-/•OH. Furthermore, degradation kinetics were strongly correlated with soil organic matter (SOM) contents than iron minerals. Combining a newly developed in situ fluorescence detector of reductive radicals with quenching experiments, we showed that for soils with high, medium, and low SOM contents, dominant reactive species switched from singlet oxygen/semiquinone radicals to SO4•-/•OH and then to COO•- (contribution increased from 30.8 to 66.7%), yielding superior HCH degradation. Validation experiments using SOM model compounds highlighted critical roles of redox-active moieties, such as phenolic - OH and quinones, in radical formation and conversion. Our study provides insights into environmental behaviors related to radical activation of persulfate in a broader soil horizon and inspiration for more advanced reduction technologies.

γ-Oryzanol from Rice Bran Antagonizes Glutamate-Induced Excitotoxicity in an In Vitro Model of Differentiated HT-22 Cells.

The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance brain function, but more research is needed to determine its potential as a treatment for vascular dementia. This study investigated if γ-oryzanol can delay or improve glutamate neurotoxicity in an in vitro model of differentiated HT-22 cells and explored its neuroprotective mechanisms. The differentiated HT-22 cells were treated with 0.1 mmol/L glutamate for 24 h then given γ-oryzanol at appropriate concentrations or memantine (10 µmol/L) for another 24 h. Glutamate produced reactive oxygen species and depleted glutathione in the cells, which reduced their viability. Mitochondrial dysfunction was also observed, including the inhibition of mitochondrial respiratory chain complex I activity, the collapse of mitochondrial transmembrane potential, and the reduction of intracellular ATP levels in the HT-22 cells. Calcium influx triggered by glutamate subsequently activated type II calcium/calmodulin-dependent protein kinase (CaMKII) in the HT-22 cells. The activation of CaMKII-ASK1-JNK MAP kinase cascade, decreased Bcl-2/Bax ratio, and increased Apaf-1-dependent caspase-9 activation were also observed due to glutamate induction, which were associated with increased DNA fragmentation. These events were attenuated when the cells were treated with γ-oryzanol (0.4 mmol/L) or the N-methyl-D-aspartate receptor antagonist memantine. The results suggest that γ-oryzanol has potent neuroprotective properties against glutamate excitotoxicity in differentiated HT-22 cells. Therefore, γ-oryzanol could be a promising candidate for the development of therapies for glutamate excitotoxicity-associated neurodegenerative diseases, including vascular dementia.

Zinc-Doped BiOBr Hollow Microspheres for Enhanced Visible Light Photocatalytic Degradation of Antibiotic Residues.

Photocatalysis represents an effective technology for environmental remediation. Herein, a series of Zn-doped BiOBr hollow microspheres are synthesized via one-pot solvothermal treatment of bismuth nitrate and dodecyl ammonium bromide in ethylene glycol along with a calculated amount of zinc acetate. Whereas the materials morphology and crystal structure remain virtually unchanged upon Zn-doping, the photocatalytic performance toward the degradation of ciprofloxacin is significantly improved under visible light irradiation. This is due to the formation of a unique band structure that facilitates the separation of photogenerated electron-hole pairs, reduced electron-transfer resistance, and enhanced electron mobility and carrier concentration. The best sample consists of a Zn doping amount of 1%, which leads to a 99.2% degradation rate of ciprofloxacin under visible photoirradiation for 30 min. The resulting photocatalysts also exhibit good stability and reusability, and the degradation intermediates exhibit reduced cytotoxicity compared to ciprofloxacin. These results highlight the unique potential of BiOBr-based photocatalysts for environmental remediation.