ABSTRACT
Genetic screening of newborns for deafness plays an important role in elucidating the etiology of deafness, diagnosing it early, and intervening in it. Genetic screening of newborns has been conducted for 11 years in Beijing. It started with a chip to screen for 9 variants of 4 genes in 2012; the chip screened for 15 variants of those genes in 2018, and it now screens for 23 variants of those genes. In the current study, a comparative analysis of three screening protocols and follow-up for infants with pathogenic variants was performed. The rates of detection and hearing test results of infants with pathogenic variants were analyzed. Subjects were 493,821 infants born at 122 maternal and child care centers in Beijing from April 2012 to August 2023. Positivity increased from 4.599% for the chip to screen for 9 variants to 4.971% for the chip to screen for 15 variants, and further to 11.489% for the chip to screen for 23 variants. The carrier frequency of the GJB2 gene increased from 2.489% for the chip to screen for 9 variants and 2.422% for the chip to screen for 15 variants to 9.055% for the chip to screen for 23 variants. The carrier frequency of the SLC26A4 gene increased from 1.621% for the chip to screen for 9 variants to 2.015% for the chip to screen for 15 variants and then to 2.151% for the chip to screen for 23 variants. According to the chip to screen for 9 variants and the chip to screen for 15 variants, the most frequent mutant allele was c.235delC. According to the chip to screen for 23 variants, the most frequent mutant allele was c.109G>A. The chip to screen for 15 variants was used to screen 66.67% (14/21) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. The chip to screen for 23 variants was used to screen 92.98% (53/57) of newborns with biallelic variants in the GJB2 gene (52 cases were biallelic c.109G>A) and 25% (1/4) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. Among the infants with pathogenic variants (biallelic variants in GJB2 or SLC26A4), 20.66% (25/121) currently have normal hearing. In addition, 34.62% (9/26) of newborns who passed the hearing screening were diagnosed with hearing loss. Findings indicate that a growing number of newborns have benefited, and especially in the early identification of potential late-onset hearing loss, as the number of screening sites has increased. Conducting long-term audiological monitoring for biallelic variants in individuals with normal hearing is of paramount significance.
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Emodin (EMO) has the effect of anti-cholestasis induced by alpha-naphthylisothiocyanate (ANIT). But its mechanism is still unclear. The farnesoid X receptor (Fxr) is the master bile acid nuclear receptor. Recent studies have reported that Sirtuin 1 (Sirt1) can regulate the activities of Fxr. The purpose of the current study was to investigate the mechanism of EMO against ANIT-induced liver injury based on Sirt1/Fxr signaling pathway. The ANIT-induced cholestatic rats were used with or without EMO treatment. Serum biochemical indicators, as well as liver histopathological changes were examined. The genes expressions of Sirt1, Fxr, Shp, Bsep and Mrp2 were detected. The expressions of Sirt1, Fxr and their downstream related genes were investigated in vitro. The results showed that EMO significantly alleviated ANIT-induced liver injury in rats, and increased Sirt1, Fxr, Shp, Bsep and Mrp2 gene expression in liver, while decreased the expression of Cyp7a1. EMO significantly activated Fxr, while Sirt1 inhibitor and Sirt1 gene silencing significantly reduced Fxr activity in vitro. Collectively, EMO in the right dose has a protective effect on liver injury induced by ANIT, and the mechanism may be through activation of Fxr by Sirt1, thus regulating bile acid metabolism, and reducing bile acid load in hepatocytes.
Subject(s)
1-Naphthylisothiocyanate , Cholestasis , Emodin , Receptors, Cytoplasmic and Nuclear , Signal Transduction , Sirtuin 1 , Animals , Sirtuin 1/metabolism , Sirtuin 1/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/drug effects , Emodin/pharmacology , Emodin/therapeutic use , Cholestasis/metabolism , Cholestasis/drug therapy , Cholestasis/pathology , Rats , Male , 1-Naphthylisothiocyanate/toxicity , Liver/metabolism , Liver/drug effects , Liver/pathology , Liver/injuries , Bile Acids and Salts/metabolism , Humans , Rats, Sprague-Dawley , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Gene Expression Regulation/drug effects , Hep G2 CellsABSTRACT
'Duli' (Pyrus betulifolia Bunge) is one of the main rootstocks of pear trees in China. Gibberellin (GA) is a key plant hormone and the roles of GA in nitrate (NO3-) uptake and metabolism in plants remain unclear. In this study, we investigated the effects of exogenous GA3 on the N metabolism of 'Duli' seedlings under NO3- deficiency. The results showed that exogenous GA3 significantly improves 'Duli' growth under NO3- deficiency. On the one hand, GA3 altered the root architecture, increased the content of endogenous hormones (GA3, IAA, and ZR), and enhanced photosynthesis; on the other hand, it enhanced the activities of N-metabolizing enzymes and the accumulation of N, and increased the expression levels of N absorption (PbNRT2) and the metabolism genes (PbNR, PbGILE, PbGS, and PbGOGAT). However, GA3 did not delay the degradation of chlorophyll. Paclobutrazol had the opposite effect on growth. Overall, GA3 can increase NO3- uptake and metabolism and relieve the growth inhibition of 'Duli' seedlings under NO3- deficiency.
Subject(s)
Gibberellins , Nitrates , Nitrogen , Pyrus , Seedlings , Seedlings/metabolism , Seedlings/growth & development , Seedlings/drug effects , Nitrates/metabolism , Gibberellins/metabolism , Nitrogen/metabolism , Pyrus/metabolism , Pyrus/genetics , Pyrus/growth & development , Pyrus/drug effects , Gene Expression Regulation, Plant/drug effects , Photosynthesis/drug effects , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/drug effects , Plant Growth Regulators/metabolism , Chlorophyll/metabolismABSTRACT
Gene therapy for monogenic auditory neuropathy (AN) has successfully improved hearing function in target gene-deficient mice. Accurate genetic diagnosis can not only clarify the etiology but also accurately locate the lesion site, providing a basis for gene therapy and guiding patient intervention and management strategies. In this study, we collected data from a family with a pair of sisters with prelingual deafness. According to their auditory tests, subject â ¡-1 was diagnosed with profound sensorineural hearing loss (SNHL), â ¡-2 was diagnosed with AN, â -1 was diagnosed with high-frequency SNHL, and â -2 had normal hearing. Using whole-exome sequencing (WES), one nonsense mutation, c.4030C>T (p.R1344X), and one missense mutation, c.5000C>A (p.A1667D), in the OTOF (NM_001287489.1) gene were identified in the two siblings. Their parents were heterozygous carriers of c.5000C>A (father) and c.4030C>T (mother). We hypothesized that c.5000C>A is a novel pathogenic mutation. Thus, subject â ¡-1 should also be diagnosed with AN caused by OTOF mutations. These findings not only expand the OTOF gene mutation spectrum for AN but also indicate that WES is an effective approach for accurately diagnosing AN.
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Objective:To analyze the mutation spectrum of 23-site chip newborn deafness genetic screening in Beijing, and to provide basis for genetic counseling and clinical diagnosis and treatment. Methods:The study included 21 006 babies born in Beijing from December 2022 to June 2023. All subjects underwent newborn deafness genetic screening in Beijing Tongren Hospital, covering 23 variants in 4 genes, the GJB2 geneï¼c.35delG, c.176_191del16, c.235delC, c.299_300delAT, c.109G>A, c.257C>G, c.512insAACG, c.427C>T, c.35insGï¼, SLC26A4 geneï¼c.919-2A>G, c.2168A>G, c.1174A>T, c.1226G>A, c.1229C>T, c.1975G>C, c.2027T>A, c.589G>A, c.1707+5G>A, c.917insG, c.281C>Tï¼, Mt12SrRNAï¼m.1555A>G, m.1494C>Tï¼ and GJB3 geneï¼c.538C>Tï¼. The mutation detection rate and allele frequency were analyzed. Results:The overall mutation detection rate was 11.516%ï¼2 419/21 006ï¼, with the GJB2 gene being the most frequently involved at 9.097%ï¼1 911/21 006ï¼, followed by the SLC26A4 gene at 2.123%ï¼446/21 006ï¼, the GJB3 gene at 0.362%ï¼76/21 006ï¼ and Mt12SrRNA at 0.176%ï¼37/21 006ï¼. Among the GJB2 genes, c.109G>A and c.235delC mutation detection rates were the highest, with 6.579%ï¼1 382/21 006ï¼ and 1.795%ï¼377/21 006ï¼, respectively. Of the SLC26A4 genes, c.919-2A>G and c.2168A>G had the highest mutation rates of 1.423%ï¼299/21 006ï¼ and 0.233%ï¼49/21 106ï¼, respectively. Regarding the allele frequency, GJB2 c.109G>A was the most common variant with an allele frequency of 3.359%ï¼1 411/42 012ï¼, followed by the GJB2 c.235delC at 0.897%ï¼377/42 012ï¼ and the SLC26A4 c.919-2A>G at 0.719%ï¼302/42 012ï¼. Conclusion:23-site chip newborn deafness genetic screening in Beijing showed that GJB2 c.109G>A mutation detection rate and allele frequency were the highest. This study has enriched the epidemiological data of 23-site chip genetic screening mutation profiles for neonatal deafness, which can provide evidence for clinical practice.
Subject(s)
Deafness , Hearing Loss , Infant , Infant, Newborn , Humans , Connexins/genetics , Connexin 26/genetics , Deafness/genetics , Deafness/diagnosis , DNA Mutational Analysis , Sulfate Transporters/genetics , Genetic Testing , Mutation , Hearing Loss/genetics , Neonatal Screening , ChinaABSTRACT
Hearing loss is the third most prevalent physical condition affecting communication, well-being, and healthcare costs. Sensorineural hearing loss often occurs first in the high-frequency region (basal turn), then towards the low-frequency region (apical turn). However, the mechanism is still unclear. Supporting cells play a critical role in the maintenance of normal cochlear function. The function and supporting capacity of these cells may be different from different frequency regions. Hensen's cells are one of the unique supporting cell types characterized by lipid droplets (LDs) in the cytoplasm. Here, we investigated the morphological and gene expression differences of Hensen's cells along the cochlear axis. We observed a gradient change in the morphological characteristics of Hensen's cells along the cochlear tonotopic axis, with larger and more abundant LDs observed in apical Hensen's cells. Smart-seq2 RNA-seq revealed differentially expressed genes (DEGs) between apical and basal Hensen's cells that clustered in several pathways, including unsaturated fatty acid biosynthesis, cholesterol metabolism, and fatty acid catabolism, which are associated with different energy storage capacities and metabolic potential. These findings suggest potential differences in lipid metabolism and oxidative energy supply between apical and basal Hensen's cells, which is consistent with the morphological differences of Hensen's cells. We also found differential expression patterns of candidate genes associated with hereditary hearing loss (HHL), noise-induced hearing loss (NIHL), and age-related hearing loss (ARHL). These findings indicate functional heterogeneity of SCs along the cochlear axis, contribute to our understanding of cochlear physiology and provide molecular basis evidence for future studies of hearing loss.
Subject(s)
Sequence Analysis, RNA , Animals , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/pathology , Lipid Metabolism/genetics , Cochlea/pathology , Cochlea/metabolism , Lipid Droplets/metabolism , HumansABSTRACT
Despite great efforts that have been made, photocatalytic carbon dioxide (CO2) reduction still faces enormous challenges due to the sluggish kinetics or disadvantageous thermodynamics. Herein, cadmium sulfide quantum dots (CdS QDs) were loaded onto carbon, oxygen-doped boron nitride (BN) and encapsulated by titanium carbide (Ti3C2, MXene) layers to construct a ternary composite. The uniform distribution of CdS QDs and the tight interfacial interaction among the three components could be achieved by adjusting the loading amounts of CdS QDs and MXene. The ternary 100MX/CQ/BN sample gave a productive rate of 2.45 and 0.44 µmol g-1 h-1 for carbon monoxide (CO) and methane (CH4), respectively. This CO yield is 1.93 and 6.13 times higher than that of CdS QDs/BN and BN counterparts. The photocatalytic durability of the ternary composite is significantly improved compared with CdS QDs/BN because MXene can protect CdS from photocorrosion. The characterization results demonstrate that the excellent CO2 adsorption and activation capabilities of BN, the visible light absorption of CdS QDs, the good conductivity of MXene and the well-matched energy band alignment jointly promote the photocatalytic performance of the ternary catalyst.
ABSTRACT
Phosphors with narrow-band green emissions and high photoluminescent quantum efficiency (PLQY) are significantly required for backlighting displays with wider color gamut. In this work, two centimeter-sized manganese (II) halide single crystals TMG2 MnCl4 and TMG2 MnBr4 (TMG = 1,1,3,3-tetramethylguanidine) are synthesized, exhibiting bright narrow-band green emissions with high PLQYs up to 62% and 90%, respectively. The narrow-band green light emission is located at 520 nm with a full-width at half-maximum (FWHM) of only 57 nm. The photoluminescence mechanisms of two single crystals are elaborated. Two white-light-emitting diodes for backlighting displays (BD-WLEDs) based on them are fabricated, exhibiting the widest color gamut of 122% National Television Standards Committee (NTSC), and a luminous efficacy reached ≈93 lm W-1 with excellent luminescence stability at high temperatures. These properties indicate the potential applications of tetrahedral manganese (II) hybrids in wide-color gamut backlighting displays.
ABSTRACT
Universal newborn hearing screening (UNHS) and audiological diagnosis are crucial for children with congenital hearing loss (HL). The objective of this study was to analyze hearing screening techniques, audiological outcomes and risk factors among children referred from a UNHS program in Beijing. A retrospective analysis was performed in children who were referred to our hospital after failing UNHS during a 9-year period. A series of audiological diagnostic tests were administered to each case, to confirm and determine the type and degree of HL. Risk factors for HL were collected. Of 1839 cases, 53.0% were referred after only transient evoked otoacoustic emission (TEOAE) testing, 46.1% were screened by a combination of TEOAE and automatic auditory brainstem response (AABR) testing, and 1.0% were referred after only AABR testing. HL was confirmed in 55.7% of cases. Ears with screening results that led to referral experienced a more severe degree of HL than those with results that passed. Risk factors for HL were identified in 113 (6.1%) cases. The main risk factors included craniofacial anomalies (2.7%), length of stay in the neonatal intensive care unit longer than 5 days (2.4%) and birth weight less than 1500 g (0.8%). The statistical data showed that age (P < 0.001) and risk factors, including craniofacial anomalies (P < 0.001) and low birth weight (P = 0.048), were associated with the presence of HL. This study suggested that hearing screening plays an important role in the early detection of HL and that children with risk factors should be closely monitored.
Subject(s)
Evoked Potentials, Auditory, Brain Stem , Neonatal Screening , Infant, Newborn , Child , Humans , Beijing/epidemiology , Retrospective Studies , Neonatal Screening/methods , Hearing Tests/methods , Otoacoustic Emissions, Spontaneous/physiology , Infant, Very Low Birth WeightABSTRACT
Low-dimensional organic-inorganic metal halides (LOMHs) recently have attracted much attention due to their tunable crystal structures and excellent photoelectric properties. The configuration and arrangement of organic cations in LOMHs have significant effect on the structure of inorganic frameworks and luminescence properties. In this work, we systematically explored the "spatial effect" and "hydrogen bonding effect" of organic cations on the structure and properties of LOMHs, by synthesizing three LOMHs including (N-AD)PbCl4, (N-AD)2Pb2Br7, and (N-AD)4Pb3I12 (N-AD: N-acetylethylenediamine, C4H10N2O). Specifically, (110)-oriented two-dimensional (N-AD)PbCl4 and (N-AD)2Pb2Br7 with manifest blue-white emissions, originating from the free excitons (FEs) and self-trapped excitons (STEs), respectively. The UV-pumped light-emitting diode (LED)-based on (N-AD)2Pb2Br7 was prepared, and the highest color rendering index (CRI) and correlated color temperature (CCT) were up to 80 and 4484 K, respectively. This proves its potential application in solid-state lighting.
ABSTRACT
Organic-inorganic hybrid metal halides have attracted widespread attention due to their excellent tunability and versatility. Here, we have selected pyridinium derivatives with different substituent groups or substitution positions as the organic templating cations and obtained six 1D chain-like structures. They are divided into three types: type I (single chain), type II (double chain), and type III (triple chain), with tunable optical band gaps and emission properties. Among them, only (2,4-LD)PbBr3 (2,4-LD = 2,4-lutidine) shows an exciton-dependent emission phenomenon, ranging from strong yellow-white to weak red-white light. By comparing its photoluminescence spectrum with that of its bromate (2,4-LD)Br, it is found that the strong yellow-white emission at 534 nm mainly came from the organic component. Furthermore, through a comparison of the fluorescence spectra and lifetimes of (2,4-LD)PbBr3 and (2-MP)PbBr3 (2-MP = 2-methylpyridine) with similar structures at different temperatures, we confirm that the tunable emission of (2,4-LD)PbBr3 comes from different photoluminescent sources corresponding to organic cations and self-trapped excitons. Density functional theory calculations further reveal that (2,4-LD)PbBr3 has a stronger interaction between organic and inorganic components compared to (2-MP)PbBr3. This work highlights the importance of organic templating cations in hybrid metal halides and the new functionalities associated with them.
ABSTRACT
Concurrent screening has been proven to provide a comprehensive approach for management of congenital deafness and prevention of ototoxicity. The SLC26A4 gene is associated with late-onset hearing loss and is of great clinical concern. For much earlier detection of newborns with deafness-causing mutations in the SLC26A4 gene, the Beijing Municipal Government launched a chip for optimized genetic screening of 15 variants of 4 genes causing deafness based on a chip to screen for 9 variants of 4 genes, and 6 variants of the SLC26A4 gene have now been added. To ascertain the advantage of a screening chip including 15 variants of 4 genes, the trends in concurrent hearing and genetic screening were analyzed in 2019 and 2020. Subjects were 76,460 newborns who underwent concurrent hearing and genetic screening at 24 maternal and child care centers in Beijing from January 2019 to December 2020. Hearing screening was conducted using transiently evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAE), or the automated auditory brainstem response (AABR). Dried blood spots were collected for genetic testing and 15 variants of 4 genes, namely GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened for using a DNA microarray platform. The initial referral rate for hearing screening decreased from 3.60% (1,502/41,690) in 2019 to 3.23% (1,124/34,770) in 2020, and the total referral rate for hearing screening dropped form 0.57% (236/41,690) in 2019 to 0.54% (187/34,770) in 2020, indicating the reduced false positive rate of newborn hearing screening and policies to prevent hearing loss conducted by the Beijing Municipal Government have had a significant effect. Positivity according to genetic screening was similar in 2019 (4.970%, 2,072/41,690) and 2020 (4.863%,1,691/34,770), and the most frequent mutant alleles were c.235 del C in the GJB2 gene, followed by c.919-2 A > G in the SLC26A4 gene, and c.299 del AT in the GJB2 gene. In this cohort study, 71.43% (5/7) of newborns with 2 variants of the SLC26A4 gene were screened for newly added mutations, and 28.57% (2/7) of newborns with 2 variants of the SLC26A4 gene passed hearing screening, suggesting that a screening chip including 15 variants of 4 genes was superior at early detection of hearing loss, and especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene. These findings have clinical significance.
Subject(s)
Deafness , Hearing Loss , Humans , Infant, Newborn , Beijing , Cross-Sectional Studies , Cohort Studies , Connexins/genetics , Connexin 26/genetics , Genetic Testing , Deafness/genetics , Hearing Loss/diagnosis , Hearing Loss/genetics , Mutation/genetics , China , Hearing , DNA Mutational AnalysisABSTRACT
Objective:To investigate the clinical audiological characteristics of children referred from maternal and child institutions and analyze the high risk factors of hearing loss, so as to provide scientific basis for further improvement of children's ear and hearing care. Methods:The subjects of this study were 868 children who were referred by maternal and child institutions in Beijing to the otology outpatient of Beijing Tongren Hospital, Capital Medical University for hearing diagnosis. All subjects underwent acoustic immittance, auditory brainstem response, distortion products otoacoustic emission and other audiological tests. Children were divided into groups according to the age of diagnosis: 0-<3 months groupï¼242 casesï¼, 3-<6 months groupï¼328 casesï¼, 6-<12 months groupï¼180 casesï¼, ≥12 months groupï¼118 casesï¼, the results of hearing diagnosis, hearing loss degree and types, the relationship between high risk factors and hearing loss in each group were compared and analyzed. Results:The age of diagnosis of 868 children wasï¼7.13±8.29ï¼ months. 488 cases with hearing loss accounted for 56.22% and 380 cases with normal hearing accounted for 43.78%. Proportion of different degree of hearing loss of 792 ears from high to low was as follows: mild, 366 earsï¼46.21%ï¼; moderate, 214 earsï¼27.02%ï¼; severe, 151 earsï¼19.07%ï¼; profound, 61 earsï¼7.70%ï¼. There were statistically significant differences in the proportion of different hearing loss degree among 0-<3 months group, 3-<6 months group, 6-<12 months group and ≥12 months groupï¼P<0.001ï¼. Pairwise comparison between groups showed that the proportion of mild hearing loss of 0-<3 months group was higher than that in the other three groupsï¼P<0.05ï¼, there was no significant difference of moderate hearing loss among all groupsï¼P>0.05ï¼, the proportion of severe hearing loss of ≥12 months group was higher than that of 0-<3 months groupï¼P<0.05ï¼. The proportion of profound hearing loss with 0-<3 months group was lower than the other three groupsï¼P<0.05ï¼. In 792 ears with hearing loss, sensorineural hearing loss accounted for 67.42%, conductive hearing loss accounted for 20.71% and mixed hearing loss accounted for 11.87%. Among 98 cases with high risk factors for hearing loss, 58 casesï¼59.18%ï¼ were diagnosed with hearing loss. The incidence of hearing loss with high risk factors ranked from high to low was: craniofacial malformationï¼93.75%ï¼, family history/congenital genetic syndromeï¼61.11%ï¼, neonatal intensive care unitï¼NICUï¼ hospitalizationï¼46.43%ï¼ and othersï¼20.00%ï¼. Conclusion:Referrals from maternal and child institutions play an important role in the early detection of children with mild to moderate sensorineural hearing loss. Children with craniofacial malformation, family history/congenital genetic syndrome, hospitalization history of NICU and other high risk factors have a high incidence of hearing loss and should be attached with great importance.
Subject(s)
Deafness , Hearing Loss, Sensorineural , Hearing Loss , Infant, Newborn , Child , Humans , Infant , Hearing Loss, Sensorineural/diagnosis , Hearing , Hearing Loss/epidemiology , Hearing Tests/methods , Evoked Potentials, Auditory, Brain Stem/physiologyABSTRACT
Rural revitalization, as a major strategy with the goal of realizing the overall development of strong agriculture industries, beautiful rural areas, and rich farmers, is an effective way of alleviating the loss of talent, land, capital, and other elements in rural areas and a possible cure for "rural diseases". However, "rural diseases" faced by villages are very different, and thus exploring suitable strategies for rural revitalization is beneficial to the implementation of rural revitalization strategies and the promotion of urban-rural integration. Based on location theory, this paper constructs a point-axis-domain three-dimensional spatial location theory model that integrates market location, traffic location, and natural location and combines the coupling coordination model to comprehensively study the vitality and development directions of Qingdao's rural areas. Results found that Qingdao's high-level and medium-high-level coupling coordination areas are the main types of coupling coordination, accounting for 45.19% and 47.48%, respectively. Based on the development status of Qingdao, this study explores development directions for rural revitalization poles as well as high-level, medium-high-level, and medium-level coupling coordination areas and suggests the following: rural revitalization poles should play a demonstration role in rural revitalization in terms of industrial development, rural civilization, social governance, public service construction, etc.; high-level coupling coordination areas should focus on building modern hi-tech agriculture and rural marine tourism industries; medium-high-level coupling coordination areas should strengthen the building of satellite towns and promote industrial transformation and upgrading; medium-level coupling coordination areas should actively develop ecological environment conservation models and establish a characteristic mountainous eco-tourism industry. Thus, the findings provide important scientific reference for the implementation of rural revitalization.
Subject(s)
Industrial Development , Rural Population , Humans , Cities , China , AgricultureABSTRACT
White-light emissive organic-inorganic hybrid metal halides (MHs) have shown promising potential applications in solid-state lighting. As one-dimensional (1D) MHs for white-light emission remain rare and the key role of halogen regulation in 1D hybrid MHs for broadband emission (BE) has not been well established yet, herein, we report a family of 1D hybrid MHs TMGPbX3 (TMG = 1,1,3,3-tetramethylguanidine, X = Cl-, Br-, or I-) to systematically explore the influence of halogen on crystal structures and photoluminescence (PL) properties in 1D organic-inorganic hybrid MHs. Under ultraviolet excitation, TMGPbBr3 and TMGPbI3 exhibit BE originating from self-trapped excitons (STEs), while TMGPbCl3 manifests the special blue-white dual emission, which is contributed by STEs in inorganic frameworks and free excitons (FEs) in the organic component. Different emission mechanisms of three 1D MHs are well demonstrated and compared. With a PL quantum yield (PLQY) up to 11.67%, a white light-emitting diode (WLED) based on TMGPbCl3 was fabricated to show its valuable application in solid-state lighting.
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BACKGROUND: This study aimed to assess the quality of global guidelines or consensus statements for newborn and childhood hearing screening, as well as to compare various guidelines between other countries and China. METHODS: A PROSPERO registered systematic review (number CRD42021242198) was conducted. Multiple electronic databases and government websites including PubMed, EMBASE, Web of Science, CENTRAL, Cochrane Library, and BMJ Best Practice were searched from inception until May 2021. The latest national and international guidelines, consensus statements, technical specifications, and recommendations regarding newborn or childhood hearing screening that were published in Chinese or English medical journals or elsewhere with the full version available online. The following information was extracted independently by two reviewers for comparative analysis: titles, authors, publication year, country, the source organization, and main key recommendations using systems for assigning the level of evidence and strength of recommendations. The quality of the guidelines was assessed by three independent reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition. Intraclass correlation coefficients (ICCs) were calculated to assess among-reviewer agreement. RESULTS: We assessed 15 newborn and 6 childhood hearing screening guidelines, respectively. Most newborn guidelines recommend the 1-3-6 guidelines and pre-discharge screening; however, the specific screening times differ. 93.33% of newborn hearing guidelines recommend "primary screening-re-screening-diagnosis-intervention" for well-babies while 73.33% of the guidelines recommend "initial screening-diagnosis-intervention" for newborns in neonatal intensive care unit (NICU); 33.33% of the newborn hearing guidelines recommended initial screening coverage of > 95% while 46.66% did not mention it. Further, 26.66% of the newborn hearing guidelines recommended a referral rate to diagnosis within 4% while 60% did not mention it. Regarding childhood hearing screening guidelines, the screening populations differed across guidelines (age range: 0-9 years); most guidelines recommend pediatric hearing screening for all preschoolers. Only 50% of the guidelines specify screening and re-screening techniques, including pure-tone hearing screening, OAE, tympanometry, and others. The "Clarity of Presentation" domain achieved the highest mean score, and the lowest was "Editorial Independence" both in newborn and childhood guidelines. Overall score of newborn hearing screening guidelines ranged from 3 (2018 Europe) to 7 (2019 America), with an average score of 5.33. Average score of childhood hearing screening guidelines was 4.78, with the score ranging from 4 (2017 England, 2012 Europe, 2016 WHO) to 6.67 (2011 America). ICC analysis revealed excellent agreement across 21 guidelines (> 0.75). CONCLUSIONS: These findings indicated newborn hearing screening guidelines had superior quality over childhood ones. Comparative analysis suggested that recommendations of the Chinese newborn and pediatric hearing screening protocols are consistent with the mainstream international opinion. Moreover, this analysis demonstrated that "Editorial Independence" and "Stakeholder Involvement" have the greatest opportunities for improvement. These results may help to advance the quality of hearing screening guidelines in clinical practice and guide evidence-based updates.
Subject(s)
Hearing Tests , Mass Screening , Child , Child, Preschool , China , Hearing , Hearing Tests/methods , Humans , Infant , Infant, Newborn , Referral and ConsultationABSTRACT
BACKGROUND: The accumulation of neurotoxic amyloid-beta (Aß) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aß levels through changes in blood Aß concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aß peptides. However, the mechanism by which Aß peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. RESULTS: In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aß1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aß1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aß1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aß1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important "carrier" for the transport of Aß1-42 from the blood to the tissues, including liver and brain. CONCLUSIONS: This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.
Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/metabolism , Liver-Specific Organic Anion Transporter 1/metabolism , Peptide Fragments/metabolism , Alzheimer Disease/chemically induced , Amyloid beta-Peptides/toxicity , HEK293 Cells , Humans , Peptide Fragments/toxicityABSTRACT
The fully inorganic perovskite lead cesium bromide single crystal (CsPbBr3 SC) is considered as an excellent candidate semiconductor for photodetectors because of its superior humidity resistance, thermal stability, and light stability compared with organic-inorganic hybrid perovskites as well as its photoelectric properties such as large light absorption coefficient and ultralong carrier migration distance. In this Letter, we utilize the inverse temperature solubility of CsPbBr3 in ternary solvents to grow large-sized CsPbBr3 SCs. By the use of the (101) plane, CsPbBr3 SC-based photodetectors are fabricated, which exhibit excellent polarized light response characteristics. The photocurrent relies on the polarization angle in a sinusoidal fashion and shows strong anisotropic optoelectronic properties. The photodetection performance perpendicular to the y axis is significantly higher than that parallel to the y axis, and the dichroic ratio under 405 nm illumination at a bias voltage of 1 V reaches 2.65. The experimental results are consistent with the results of first-principles calculations.
ABSTRACT
Objective:To analyze the current status of newborn deafness gene screening from 2016 to 2017 in multiple regions of China, and to provide a reference for further promotion and application. Method:The "newborn deafness gene screening questionnaire" was sent to 41 institutions in eastern, central and western China after expert demonstration. The survey content included status of genetic screening, screening methods, the number of screenings, and the status of positive detections from January 1st, 2016 to December 31th, 2017. Each institution returned the questionnaire, the investigator conducted data verification and quality sampling. Finally, we performed analysis of screening methods and the positive detection rate of each gene on questionnaires with complete data. Result:Forty-one questionnaires were sent out and 41 were returned, the questionnaire return rate was 100%, in which 12 questionnaires were complete. Of the 41 institutions, 15 carried newborn deafness gene screening, with a rate of 36.59%ï¼15/41ï¼. The highest rate was in the eastï¼72.22%, 13/18ï¼, and the differences among the regions were statistically significant. As for the screening methods, among 12 questionnaires with complete data, 9 variants in 4 genes and 20 variants in 4 genes accounted for the highest proportion, both with the rate of 33.33%ï¼4/12ï¼, followed by 15 variants in 4 genesï¼25%, 3/12ï¼ and 5 variants in 3 genesï¼8.34%, 1/12ï¼. A total of 340, 521 neonates were included in the study, and 17, 036 were positive for screening, with a positive rate of 5.00%. Among them, the single heterozygous mutation rate of GJB2 gene was 2.43%ï¼8269/340, 521ï¼, the biallele mutation rate was 0.02%ï¼56/340, 521ï¼,the single heterozygous mutation rate of SLC26A4 gene was 1.99%ï¼6771/340, 521ï¼, the biallele mutation rate was 0.01%ï¼39/340, 521ï¼,the single heterozygous mutation rate of GJB3 gene was 0.33%ï¼1140/340, 521ï¼, the mitochondrial 12SrRNA gene mutation rate was 0.22%ï¼746/340, 521ï¼ and the double-gene heterozygous mutation rate was 0.004%ï¼15/340, 521ï¼. Conclusion:From 2016 to 2017, the newborn deafness gene screening is more extensive in the eastern region of China than in the central and western regions. In institutions that have carried out deafness gene screening, 9 variants in 4 genes and 20 variants in 4 genes are widely used; the GJB2 gene and SLC26A4 gene mutations are the most common. The results could provide references for areas where deafness gene screening is about to be performed.