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Near-field acoustic holography (NAH) based on compressing sensing (CS) theory enables accurate reconstruction of sound fields using a limited number of sampling points. However, the successful implementation of this technique depends on two crucial factors: (1) the appropriate selection or construction of the spatial basis and (2) an effective sparse regularization process. To enhance reconstruction performance for elongated sound sources, this paper proposes a novel sound field reconstruction method that combines prolate spheroidal wave functions (PSWFs) with the orthogonal matching pursuit (OMP) algorithm. In this method, PSWFs serve as a sparse spatial basis for representing the radiated sound field. The sparse coefficients are determined by the OMP algorithm in a linear subspace composed of basic functions that best match the residual error. The OMP algorithm effectively identifies significant components before potentially selecting incorrect ones by setting an appropriate stopping rule. Numerical simulations are conducted using a line-array source model. The results show that the proposed method can accurately reconstruct the sound pressures of the elongated source model using a relatively small number of samplings. In addition, the proposed method exhibits robustness across a wide frequency range, diverse array configurations and various sampling numbers. The experimental results further validate the feasibility and reliability of the proposed method. [ABSTRACT FROM AUTHOR]

Near-field acoustic holography (NAH) is an effective tool for realizing accurate sound field reconstruction in three-dimensional space on the prerequisite that appropriate elementary wave functions are selected or constructed to match the characteristics of the sound sources. However, for elongated sources, common wave functions, i.e., plane, cylindrical, or spherical waves, sometimes do not perform well during the sound field projections. To solve this problem, statistically optimized near-field acoustical holography combined with prolate spheroidal wave functions is proposed. In the approach, the sound field is expanded by a series of prolate spheroidal wave functions, whose wavefronts can be set nearly conformal to the elongated sources. Based on these wave functions, fewer expansion terms are required to model the sound field, and the need for regularization can be reduced during the inverse solving process. Therefore, the accuracy of the reconstruction results can be further improved. Numerical simulations are conducted by two types of elongated source models, namely, spatially separated and extended. The results show that the proposed method can effectively reconstruct the sound pressures of elongated sources and perform robustly across a wide frequency range. Simultaneously, a designed experiment is carried out in an anechoic chamber, which demonstrates the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

Although the role of serine racemase (SR) in neuropsychiatric disorders has been extensively studied, its role in cell proliferation and differentiation remains unclear. Deletion of Srr, the encoding gene for SR, has been shown to reduce dendritic arborization and dendritic spine density in the brains of adult mice, whereas increased SR levels have been associated with differentiation in cell cultures. Previously, we demonstrated that valproic acid induces differentiation in the N2A neuroblastoma cell line, and that this differentiation is associated with increased SR expression. These observations suggest that SR may have a role in cell proliferation and differentiation. We herein found that both valproic acid and all‐trans retinoic acid induced N2A differentiation. In contrast, knockdown of SR reduced levels of differentiation, increased N2A proliferation, promoted cell cycle entry, and modulated expression of cell cycle‐related proteins. To further evaluate the effects of SR expression on cell proliferation and differentiation, we used an in vivo model of neuroblastoma in nude mice. N2A cells stably expressing scramble shRNA (Srrwt‐N2A) or specific Srr shRNA (Srrkd‐N2A) were subcutaneously injected into nude mice. The weights and volumes of Srrwt‐N2A‐derived tumors were lower than Srrkd‐N2A‐derived tumors. Furthermore, Srrwt‐N2A‐derived tumors were significantly mitigated by intraperitoneal injection of valproic acid, whereas Srrkd‐N2A‐derived tumors were unaffected. Taken together, our findings demonstrate for the first time that alterations in SR expression determine the transition between proliferation and differentiation in neural progenitor cells. Thus, in addition to its well‐established roles in neuropsychiatric disorders, our study has highlighted a novel role for SR in cell proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Vibrio vulnificus is an important zoonotic and aquatic pathogen and can cause vibriosis in humans and aquatic animals (especially farmed fish and shrimp species). Rapid and sensitive detection methods for V. vulnificus are still required to diagnose human vibriosis early and reduce aquaculture losses. Herein, we developed a rapid and sensitive diagnostic method comprising a recombinase-aided amplification (RAA) assay and the CRISPR/Cas12a system (named RAA-CRISPR/Cas12a) to detect V. vulnificus. The RAA-CRISPR/Cas12a method allows rapid and sensitive detection of V. vulnificus in 40 min without a sophisticated instrument, and the limit of detection is two copies of V. vulnificus genomic DNA per reaction. Meanwhile, the method shows satisfactory specificity toward non-target bacteria and high accuracy in the spiked blood, stool, and shrimp samples. Therefore, our proposed rapid and sensitive V. vulnificus detection method, RAA-CRISPR/Cas12a, has great potential for early diagnosis of human vibriosis and on-site V. vulnificus detection in aquaculture and food safety control. [ABSTRACT FROM AUTHOR]

Ubiquitin-specific protease (USP) 6 is a hominoid deubiquitinating enzyme previously implicated in intellectual disability and autism spectrum disorder. Although these findings link USP6 to higher brain function, potential roles for USP6 in cognition have not been investigated. Here, we report that USP6 is highly expressed in induced human neurons and that neuron-specific expression of USP6 enhances learning and memory in a transgenic mouse model. Similarly, USP6 expression regulates N-methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation and long-term depression in USP6 transgenic mouse hippocampi. Proteomic characterization of transgenic USP6 mouse cortex reveals attenuated NMDAR ubiquitination, with concomitant elevation in NMDAR expression, stability, and cell surface distribution with USP6 overexpression. USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells. Together, these results indicate that USP6 enhances NMDAR stability to promote synaptic function and cognition. This study identifies the hominoid-specific USP6 as a novel deubiquitinase of NMDA receptors, and shows that neuronal expression of human USP6 transgene enhances cognitive and synaptic function in mice, suggesting a potential role of USP6 in the evolution of human intelligence. [ABSTRACT FROM AUTHOR]

Fungicides are frequently detected in the water bodies, however, the adverse effects of these fungicides on aquatic lives remain limited. To better understand the adverse effects of amisulbrom (AML) and isoflucypram (ISO) on embryogenesis, zebrafish embryos were exposed to two different fungicides, 0.75 μM amisulbrom (AML) and 2.5 μM isoflucypram (ISO), for 72 h. Transcriptome sequencing was employed to identify differentially expressed genes (DEGs) after AML and ISO exposure. A total of 571 and 3471 DEGs were detected between the libraries of the two fungicides-treated groups and the control, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that PPAR signaling pathway, phototransduction, ribosome and p53 signaling pathway were significantly enriched in response to both AML and ISO stress. Moreover, a number of DEGs involved in tyrosine metabolism, phagosome pathway, cell cycle pathway, extracellular matrix (ECM) receptor interaction pathway, and arginine and proline metabolism were specially enriched after exposure to AML; a number of DEGs involved in notch signaling pathway, drug metabolism, alanine, aspartate and glutamate metabolism, amino-acyl−tRNA biosynthesis, and protein processing in endoplasmic reticulum were significantly enriched after exposure to ISO. These results provide novel insights into the toxicological mechanisms underlying fish's responses to fungicides. [ABSTRACT FROM AUTHOR]

Bixafen, a pyrazole-carboxamide fungicide, is a potent toxicant that may elicit multiple adverse effects in non-target organisms. However, knowledge of the mechanisms involved in developmental defects caused by bixafen in aquatic organisms remains limited. In this study, the effects of bixafen on retinal development were evaluated in embryo-larval zebrafish. We exposed zebrafish embryos to 0, 0.1, and 0.3 μM bixafen. Exposure of zebrafish embryos to bixafen caused severe retinal defects, including extreme microphthalmia and a significantly increased cell density of the ganglion cell layer (GCL). Compared with the controls, the expression levels of rod and cone photoreceptor marker genes (rho , opn1sw2 , opn1mw1 , opn1lw1 , and opn1sw1) in the outer nuclear layer (ONL) were significantly downregulated after bixafen exposure. Furthermore, bixafen caused significantly increased expression levels in the GCL marker ath5 and decreased expression levels in the inner nuclear layer (INL) markers prox1a , vsx1 , and sox2. Accordingly, we observed a significantly increased rate of cell apoptosis in the retina after bixafen exposure. Taken together, our data demonstrate that bixafen exhibits retinal developmental toxicity to zebrafish embryos/larvae, and thus, it may pose a significant environmental threat to aquatic organisms. • Bixafen caused developmental eye disorders in zebrafish embryos. • Bixafen disrupted transcription of retinal layer marker genes. • Bixafen induced microphthalmia by increasing retinal apoptosis in zebrafish. [ABSTRACT FROM AUTHOR]

Serine racemase (SR) synthesizes l-type serine to its enantimor, d -serine which participates in physiological processes and in pathological conditions. In the central nervous system, SR is highly expressed in neurons and astrocytes but expressed at relatively lower amount in microglia. However, the mechanism by which SR is highly expessed in neurons is hitherto unknown. We report that the SR mRNA and protein levels in Neuro-2a were increased by valproic acid (VPA), a neuron differentiation stimulator as well as a histone deacetylase inhibitor. SR proximal promoter contained nine putative Sp-binding elements and in the exon 1, three putative anti-oxidant elements (AREs) were conservative among human, rat, and mouse genome. The promoter constructs including 5′-, 3′-fragment, and full length fragment from mouse were individually cloned into a luciferase reporter. Using dual-luciferase assay, the promoter harboring 3′-fragment contained much lower activity than the construct containing 5′-fragment which was though resistant to VPA induction, relative to 3′-fragment. Overexpression of Sp4 or Nrf2 increased whereas knockdown of either decreased Srr mRNA and SR protein. Using site-directed mutagenesis, mutation of Sp-binding elements or AREs in the constructs significantly decreased luciferase activity of the corresponding promoter construct. With chromatin immunoprecipitation, Sp4 was demonstrated to interact directly with the Sp-binding elements whereas Nrf2 bound AREs in Srr mRNA promoter. Altogether, our study highlights that Sp4 controls constitutive expression of SR in neuron and VPA mediates SR expression in N2A cells which is associated with its effect on neuron differentiation, that is, the effect is mediated via Nrf2. • VPA increased Srr mRNA and SR protein levels due to its effect on neuron differentiation. • Sp4 maintained high level of Srr transcription in N2A cells. • Nrf2-ARE mediated elevation of SR in response to VPA induction. [ABSTRACT FROM AUTHOR]

In this paper, diamond film-coated silicon was developed to be used as a substrate in a microstrip gas chamber (MSGC) for the first time. The roughness of the composite substrate was rather low, and the resistivity was in the range of 1010–1011Ω cm. Its capacitance was very small and almost had no variation with frequency. All these results prove that the diamond film/Si composite material is a promising substrate for MSGCs. Using this composite substrate, a MSGC detector with an area of 2 × 2 cm2 was fabricated. The effects of the drift voltage and cathode voltage on the energy resolution for 5.9 keV 55Fe x-rays have been examined in detail and discussed. An energy resolution (the relative full width at half maximum of the x-ray peak) of 12.3% was achieved when the MSGC was operated at a drift voltage of −1000 V and a cathode voltage of −650 V with a gas mixture (90% Ar + 10% CH4). [ABSTRACT FROM AUTHOR]

Regulation of serine racemase (SR) occurs at transcriptional and translational levels; post-translational modification, cytosolic distribution as well as allosteric effect regulate SR activity. In this study, we report a new route of SR regulation, i.e. oxidative stress and hypermethylation of the srr (gene of SR) promoter correlate with its reduced transcription in aging rat cerebella. We first showed that the mRNA and protein level of srr were decreased in the homogenates of rat cerebellum at age 12 months compared with the counterparts from age 20 days. The reduction of SR protein level in aging cerebella was evidenced by decreased immunostaining observed in the cell body of granule cells or Purkinje cells. Staining for 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker for oxidative stress to DNA, was much stronger in granule cell or Purkinje cell nuclei from rat cerebella at 12 months compared with staining at 20 days. We further detected srr promoter hypermethylation at 12 months compared with that at 20 days by use of bisulfite sequencing PCR, coinciding with elevated protein levels of DNA methyltransferase 1 (DNMT1) in homogenates of aging cerebella. In vitro, we demonstrated that chronic treatment with the oxidant, menadione (VK3), reduced srr mRNA levels, which was reversed by the DNA demethylating agent 5-Aza-dC-2′-deoxycytidine (5-Aza-dC) in primary cerebellar granule cell cultures. Together, the in vivo and ex vivo results suggest that oxidative DNA stress and srr promoter hypermethylation are associated with reduced srr gene transcription and corresponding reduced protein expression in aging cerebella. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia-induced neuroinflammation significantly contributes to diabetic neuropathic pain (DNP), but the underlying mechanisms remain unclear., Objective: To investigate the role of Sirt3, a mitochondrial deacetylase, in hyperglycemia-induced neuroinflammation and DNP and to explore potential therapeutic interventions., Method and Results: Here, we found that Sirt3 was downregulated in spinal dorsal horn (SDH) of diabetic mice by RNA-sequencing, which was further confirmed at the mRNA and protein level. Sirt3 deficiency exacerbated hyperglycemia-induced neuroinflammation and DNP by enhancing microglial aerobic glycolysis in vivo and in vitro. Overexpression of Sirt3 in microglia alleviated inflammation by reducing aerobic glycolysis. Mechanistically, high-glucose stimulation activated Akt, which phosphorylates and inactivates FoxO1. The inactivation of FoxO1 diminished the transcription of Sirt3. Besides that, we also found that hyperglycemia induced Sirt3 degradation via the mitophagy-lysosomal pathway. Blocking Akt activation by GSK69093 or metformin rescued the degradation of Sirt3 protein and transcription inhibition of Sirt3 mRNA, which substantially diminished hyperglycemia-induced inflammation. Metformin in vivo treatment alleviated neuroinflammation and diabetic neuropathic pain by rescuing hyperglycemia-induced Sirt3 downregulation., Conclusion: Hyperglycemia induces metabolic reprogramming and inflammatory activation in microglia through the regulation of Sirt3 transcription and degradation. This novel mechanism identifies Sirt3 as a potential drug target for treating DNP., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aeromonas hydrophila is an emerging waterborne and foodborne pathogen with pathogenicity to humans and warm water fishes, which severely threatens human health, food safety and aquaculture. A novel method for the rapid, accurate, and sensitive detection of pathogenic A. hydrophila is still needed to reduce the impact on human health and aquaculture. In this work, we developed a rapid, accurate, sensitive, and visual detection method (dRAA-CRISPR/Cas12a), without elaborate instruments, integrating the dualplex recombinase-assisted amplification (dRAA) assay and CRISPR/Cas12a system to detect pathogenic A. hydrophila expressing aerA and/or hlyA virulence genes. The dRAA-CRISPR/Cas12a method has high sensitivity, which can rapidly detect (about 45 min) A. hydrophila with the limit of detection in 2 copies of genomic DNA per reaction, and has high specificity for three pathogenic A. hydrophila strains ( aerA + hlyA - , aerA - hlyA + , and aerA + hlyA + ). Moreover, dRAA-CRISPR/Cas12a method shows satisfactory practicability in the analysis of the spiked human blood and stool and fish samples. These results demonstrate that our developed pathogenic A. hydrophila detection method, dRAA-CRISPR/Cas12a, is a promising potential method for the early diagnosis of human A. hydrophila infection and on-site detection of A. hydrophila in food and aquaculture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Lu, Wu, Lin, Zheng, Lou and Xiao.)

DNA methylation is considered to play an important role in the development of diabetic retinopathy. Here, our goal was to investigate the precise role of methyl-CpG binding domain protein 2 (Mbd2) in the apoptosis of retinal ganglion cells (RGCs) in the early diabetic retina. Mbd2 was significantly upregulated after high glucose (HG) treatment and played a proapoptotic role in RGCs during HG-induced apoptosis. Combining ChIP and gene microarray datasets, the results showed that Mbd2 possessed potential binding sites for miR-345-5p, thereby elevating the expression levels of miR-345-5p via the enhancement of promoter demethylation. Activating transcription factor 1 (Atf1) played an anti-apoptotic role during the process of apoptosis in RGCs and acted as the target gene for miR-345-5p. Furthermore, the number of surviving RGCs in the diabetic retina was increased in Mbd2-knockout mice when compared with wild-type mice and the visual function became better accordingly. Collectively, our data demonstrated that the HG-induced overexpression of Mbd2 in the retina was partly responsible for the apoptosis of retinal neuronal cells through the miR-345-5p/Atf1 axis. Therefore, the targeting of Mbd2 might represent a novel therapeutic strategy for the treatment of neurodegeneration in the early diabetic retina., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Purpose: Apoptosis of the retinal ganglion cells (RGCs) can cause irreversible damage to visual function after retinal ischemia reperfusion injury (RIR). Using a lncRNA chip assay, we selected lncRNA Ttc-209 and characterized its role in RGCs during ischemia reperfusion (I/R)-induced apoptosis., Methods: We created an ischemic model of RGCs by applying Hank's balanced salt solution containing 10 µM antimycin A and 2 µM calcium ionophore for 2 hours. RIR was induced in mice by elevating the intraocular pressure to 120 mm Hg for 1 hour by cannulation of the cornea; this was followed by reperfusion. Real-time quantitative PCR was used to detect the expression levels of long noncoding RNA (lncRNA), microRNA (miRNA), and target gene mRNA. Western blotting, flow cytometry, immunofluorescent staining, and TUNEL assays were performed to detect cell apoptosis. Dual-luciferase reporter assays and FISH were used to identify endogenous competitive RNA (ceRNA) mechanisms that link lncRNAs, miRNAs, and target genes. We also used scotopic electroretinography examinations to evaluate visual function in treated mice., Results: lncRNA Ttc3-209 was significantly upregulated after I/R injury and played a proapoptotic role in RGCs during I/R-induced apoptosis. Mechanistically, lncRNA Ttc3-209 is a ceRNA that competitively binds to miR-484 and upregulates the translation of its target (Wnt8a mRNA), thus promoting apoptosis in RGCs., Conclusions: Reducing the expression of lncRNA Ttc3-209 had a protective effect against apoptosis in RGCs. This may provide a new therapeutic option for the prevention of RGC apoptosis in response to RIR injury.

Serine racemase (SR) synthesizes l-type serine to its enantimor, d-serine which participates in physiological processes and in pathological conditions. In the central nervous system, SR is highly expressed in neurons and astrocytes but expressed at relatively lower amount in microglia. However, the mechanism by which SR is highly expessed in neurons is hitherto unknown. We report that the SR mRNA and protein levels in Neuro-2a were increased by valproic acid (VPA), a neuron differentiation stimulator as well as a histone deacetylase inhibitor. SR proximal promoter contained nine putative Sp-binding elements and in the exon 1, three putative anti-oxidant elements (AREs) were conservative among human, rat, and mouse genome. The promoter constructs including 5'-, 3'-fragment, and full length fragment from mouse were individually cloned into a luciferase reporter. Using dual-luciferase assay, the promoter harboring 3'-fragment contained much lower activity than the construct containing 5'-fragment which was though resistant to VPA induction, relative to 3'-fragment. Overexpression of Sp4 or Nrf2 increased whereas knockdown of either decreased Srr mRNA and SR protein. Using site-directed mutagenesis, mutation of Sp-binding elements or AREs in the constructs significantly decreased luciferase activity of the corresponding promoter construct. With chromatin immunoprecipitation, Sp4 was demonstrated to interact directly with the Sp-binding elements whereas Nrf2 bound AREs in Srr mRNA promoter. Altogether, our study highlights that Sp4 controls constitutive expression of SR in neuron and VPA mediates SR expression in N2A cells which is associated with its effect on neuron differentiation, that is, the effect is mediated via Nrf2., Competing Interests: Declaration of competing interest The authors have found none to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To establish individualized prenatal diagnosis program for families affected with Duchenne/Becker muscular dystrophy (DMD/BMD) and different clinical background using a variety of methods., Methods: Multiplex ligation-dependent probe amplification (MLPA) was performed on 50 patients suspected for DMD/BMD. For single exon deletions of the DMD gene, PCR was used for validating the results. For those without any deletion or duplication, Sanger sequencing was used to screen for DMD gene mutations in the children and their mothers. Prenatal genetic testing was provided to female carriers using chorionic villus, amniocentesis or cord blood samples. To ensure the accuracy of diagnosis, all prenatal specimens were also subjected to linkage analysis., Results: Among the 50 patients with DMD/BMD, 23 harbored large deletions, 11 only had single exon deletions, 10 harbored duplications, and 5 had small scare mutations. No mutation was detected in one family. For 37 women undergoing prenatal diagnosis, 10 fetuses were identified as affected males, 6 were female carriers, while 21 were not found to carry any mutation. Testing of creatine kinase was consistent with the results of prenatal diagnosis. For a patient harboring exon 51 deletion, the same mutation was found in a fetus but not in their mother. The proband and fetus had inherited the same haplotype, which suggested that the mother probably has germline mosaicism for the mutation., Conclusion: Application of individualized methods for analyzing pregnant women with different clinical background can minimize the risk for giving birth to further children affected with DMD/BMD.

Objective: To analyze the clinical features and pathological mutations in 44 families affected with hearing loss from southern Zhejiang, and to provide genetic counseling and prenatal diagnosis for 6 of the families., Methods: Microarray was employed to detect c.35delG, c.176del16, c.235delC and c.299-300delAT mutations of the GJB2 gene among 228 patients. For those carrying a single heterozygous mutation, the whole coding region of the GJB2 gene was analyzed by Sanger sequencing. For prenatal diagnosis, maternal DNA contamination was excluded by application of STR analysis., Results: The microarray assay has detected 49 patients with GJB2 mutations, which included 24 homozygous c.235delC mutations, 5 compound heterozygous c.235delC/c.176del16 mutations, 2 compound heterozygous c.235delC/c.299-300delAT mutations. Respectively, 16, 1 and 1 patients have carried single heterozygous c.235delC, c.176del16, and c.299-300delAT mutation. For the 16 patients, 7, 1, 1, 2, and 3 were detected by Sanger sequencing with a second heterozygous mutation of c.109G>A (2 of which were in conjunction with heterozygous c.176del16 and c.299-300delAT mutations), c.230G>A, c.427C>T, c.508-511 dupAACG, 79G>A+341A>G, respectively. Prenatal diagnosis revealed a compound heterozygous mutation in a fetus, heterozygous mutations in 4 fetuses, and no mutation of the GJB2 gene in 1 fetus., Conclusion: The proportion of carriers for GJB2 gene mutations in patients with hearing loss from southern Zhejiang has reached 21.5%. The c.235delC, c.176del16, and compound c.299-300delAT and c.109G>A mutations can cause moderate to severe hearing loss. In most affected families, Heterozygous mutations may be identified by sequencing the whole coding region of the GJB2 gene. Genetic analysis and prenatal diagnosis can prevent birth of further affected children.

By using the fuzzy min-max neural network, the quantitative structure-activity relationship (QSAR) of mutagenicity is studied. With the established QSAR model, the mutagenicity is predicted and the results showed that QASR is superior to linear-regression model. Further discussion on the models and the results is presented in this paper.