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The identification of ecosystem health and its influencing factors is crucial to the sustainable management of ecosystems and ecosystem restoration. Although numerous studies on ecosystem health have been carried out from different perspectives, few studies have systematically investigated the spatiotemporal heterogeneity between ecosystem health and its influencing factors. Considering this gap, the spatial relationships between ecosystem health and its factors concerning climate, socioeconomic, and natural resource endowment at the county level were estimated based on a geographically weighted regression (GWR) model. The spatiotemporal distribution pattern and driving mechanism of ecosystem health were systematically analysed. The results showed the following: (1) the ecosystem health level in Inner Mongolia spatially increases from northwest to southeast, displaying notable global spatial autocorrelation and local spatial aggregation. (2) The factors influencing ecosystem health exhibit significant spatial heterogeneity. Annual average precipitation (AMP) and biodiversity (BI) are positively correlated with ecosystem health, and annual average temperature (AMT) and land use intensity (LUI) are estimated to be negatively correlated with ecosystem health. (3) Annual average precipitation (AMP) significantly improves ecosystem health, whereas annual average temperature (AMT) significantly worsens eco-health in the eastern and northern regions. LUI negatively impacts ecosystem health in western counties (such as Alxa, Ordos, and Baynnur). This study contributes to extending our understanding of ecosystem health depending on spatial scale and can inform decision-makers about how to control various influencing factors to improve the local ecology under local conditions. Finally, this study also proposes some relevant policy suggestions and provides effective ecosystem preservation and management support in Inner Mongolia.

Studying the impact of large-scale ecological projects, such as the Grain-for-Green Program (GGP), on ecosystem services (ES) is currently a frontier and hot topic of ecological research. The GGP can directly change land use and land cover, thus affecting ES. By comparing the changes of ecosystem service value (ESV) and ecosystem service scarcity value (ESSV) in Qinghai before and after the implementation of the GGP, this paper clarified the impact of the GGP on Qinghai from the angles of ecology and economics. This paper quantified and evaluated the land use dynamics, ESV, and ESSV in Qinghai from 1995 to 2020. The results showed that in the past 25 years, the total annual Normalized Difference Vegetation Index (NDVI) of Qinghai showed a trend of sustained growth. From 1995 to 2020, the ESV increased by 6.80%. After considering supply and demand, the ESSV showed a continuous upward trend, increasing by 719.38%. After implementation of the GGP, the increase of NDVI inhibited the increase of the ESSV. These findings from evaluation of the effect of the GGP implementation provide a theoretical basis for future policy implementation and, in particular, a reference for the evaluation of the ESV and the ESSV in Qinghai.

SummaryOlfactory neuroblastoma (ONB) is an uncommon malignant tumor known to originate from the olfactory epithelial. The complex tumor ecosystem of this pathology remained unclear. Here, we explored the cellular components with ONB tumors based on scRNA profiles of 96,325 single-cells derived from 10 tumors and 1 olfactory mucosa sample. We discovered 11 major cell types, including 6 immune cell, 3 stromal cell subtypes and epithelial cluster in the tumor microenvironment (TME), and identified 5 common expression programs from malignant epithelial cells. We analyzed subclusters of TME and the interactions among different cell types in the TME. An innovative three-classification of ONB was established via scRNA analysis. Markers for categorizing tumor samples into new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be inferred according to the molecular features of three tumor types. Relative abundance of immunosuppressive TAMs indicated the benefits of immunotherapies targeting myeloid cells.

One new 2-arylbenzo[b]furan named iteafuranal F (1) as well as two known analogues (2–3) were isolated from the 95% EtOH extract of aerial parts of Itea omeiensis. Their chemical structures were constructed based on extensive analyses of UV, IR, 1D/2D NMR and HRMS spectra. Antioxidant assays revealed significant superoxide anion radical scavenging capacity of 1 with IC50 value of 0.66 mg/mL, which was comparable to the efficiency of positive control of luteolin. In addition, the preliminary MS fragmentation patterns in negative ion mode were established to distinguish 2-arylbenzo[b]furans with C-10 in different oxidation states: the characteristic loss of CO molecule [M-H-28]- was observed for 3-formyl-2-arylbenzo[b]furans, and the loss of CH2O fragment [M-H-30]- for 3-hydroxymethyl-2-arylbenzo[b]furans, and the loss of CO2 fragment [M-H-44]- for 2-arylbenzo[b]furan-3-carboxylic acids.

The identification of ecosystem health and its influencing factors is crucial to sustainable management of ecosystem and ecosystem restoration. In spite of numerous studies on ecosystem health have been carried out in different perspectives, few studies have investigated the spatiotemporal heterogeneity between ecosystem health and its influencing factors systematically. Considering this gap, the spatial relationships between ecosystem health and its factors concerning climate, socioeconomic and natural resource endowment at the county level were estimated based on a geographically weighted regression (GWR) model. The spatio-temporal distribution pattern and driving mechanism of ecosystem health were systematically analyzed. Results showed that:(1)The ecosystem health level in Inner Mongolia spatially increases from northwest to southeast, displaying notable global spatial autocorrelation and local spatial aggregation.(2)The factors influencing ecosystem health exhibit significant spatial heterogeneity. Annual average precipitation (AMP),biodiversity(BI) was positively correlated with ecosystem health, annual average temperature(AMT) and land use intensity(LUI)are estimated to be negative.(3) Annual average precipitation (AMP) significantly improves ecosystem health, whereas annual average temperature (AMT) significantly worsens eco-health in the eastern and northern regions. LUI negatively impacts ecosystem health in western counties (such as Alxa, Ordos, and Baynnur).This study contributes to extending our understanding of ecosystem health depend on spatial scale, and could inform decision-makers about how to control various influencing factors to improve the local ecology under local conditions. Finally, this study also proposed some relevant policy suggestions and provide effective ecosystem preservation and management support in Inner Mongolia.

Hearing loss is the most common sensory neural disorder in humans, and according to a WHO estimation, 5.5% (466 million) of people worldwide have disabling hearing loss. In this study, a Chinese family with prelingual sensorineural hearing loss was investigated. The affected individuals showed moderately severe hearing loss at all frequencies. Using target genome enrichment and high-throughput sequencing, the homozygous variant c.2372del; p.(Ser791fs) was identified in PDZD7. This variant lies in exon 15 of PDZD7 and results in a frame shift followed by an early stop codon. It is classified as pathogenic according to the ACMG/AMP guidelines and ClinGen specifications. Our study expands the pathogenic variant spectrum of PDZD7 and strengthens the clinical importance of this gene in patients with moderately severe hearing loss.

Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral auditory circuity are still lacking. Here, we developed cochlear organoids with functional peripheral auditory circuity in a staging three-dimensional (3D) co-culture system by initially reprogramming cochlear progenitor cells (CPCs) with increased proliferative potency that could be long-term expanded, then stepwise inducing the differentiation of cochlear HCs, as well as the outgrowth of neurites from SGNs. The function of HCs and synapses within organoids was confirmed by a series of morphological and electrophysiological evaluations. Single-cell mRNA sequencing revealed the differentiation trajectories of CPCs toward the major cochlear cell types and the dynamic gene expression during organoid HC development, which resembled the pattern of native HCs. We established the cochlear organoids with functional synapses for the first time, which provides a platform for deciphering the mechanisms of sensorineural hearing loss.

Background Hereditary hearing loss is a heterogeneous class of disorders that exhibits various patterns of inheritance and involves many genes. Variants in the EYA4 gene in DFNA10 are known to lead to postlingual, progressive, autosomal dominant nonsyndromic hereditary hearing loss. Patients and methods We collected a four-generation Chinese family with autosomal-dominant nonsyndromic hearing loss (ADNSHL). We applied targeted next-generation sequencing (TNGS) in three patients of this pedigree and whole-genome sequencing (WGS) in the proband. The intrafamilial cosegregation of the variant and the deafness phenotype were confirmed by PCR, gap-PCR and Sanger sequencing. Results A novel CNV deletion at 6q23 in exons 8–11 of the EYA4 gene with a 10 bp insertion was identified by TNGS and WGS and segregated with the ADNSHL phenotypes. Conclusions Our results expanded the variant spectrum and genotype‒phenotype correlation of the EYA4 gene and autosomal dominant nonsyndromic hereditary hearing loss in Chinese Han individuals. WGS is an accurate and effective method for verifying the genomic features of CNVs.

The pathogenic variants in KCNQ4 cause DFNA2 nonsyndromic hearing loss. However, the understanding of genotype-phenotype correlations between KCNQ4 and hearing is limited. Here, we identified a novel KCNQ4 mutation p.G228D from a Chinese family, including heterozygotes characterized by high-frequency hearing loss that is progressive across all frequencies and homozygotes with more severe hearing loss. We constructed a novel murine model with humanized homologous Kcnq4 mutation. The heterozygotes had mid-frequency and high-frequency hearing loss at 4 weeks, and moved toward all frequencies hearing loss at 12 weeks, while the homozygotes had severe-to-profound hearing loss at 8 weeks. The degeneration of outer hair cells (OHCs) was observed from basal to apical turn of cochlea. The reduced K

Rapid economic development and accelerated urbanization have seriously affected the development of traditional ethnic villages in China. We used the minimum cumulative resistance (MCR) model based on land use, landscape pattern, and ecosystem service value (ESV) to evaluate the spatio-temporal dynamics of sustainable development in Hani traditional ethnic villages from 1995 to 2020. By analyzing changes in sustainability indicators in the Hani area and different buffer zones, this paper aims to assess the impact of ethnic villages in the Hani Area on sustainable development and provide recommendations for the sustainable development of traditional ethnic Hani villages. The results indicated that: (1) The area of construction land and landscape fragmentation in the Hani area significantly increased and the value of ecosystem services and levels of sustainable development decreased each year during the study period; (2) The area of cropland in the 2 km buffer zone of the traditional ethnic villages increased, the degree of landscape fragmentation, the value of ecosystem services, and the level of sustainable development were lower than in the 4 km buffer zone during the study period. This is due to population increases in traditional ethnic Hani villages, as well as the intensive reclamation of cropland, increased construction land, and landscape fragmentation. We suggest that the Hani should implement scientific land planning and management policies to protect the local ecosystem and realize the sustainable development of traditional ethnic Hani villages.

Kearns–Sayre Syndrome (KSS) is a severe mitochondrial disorder involving the central nervous system, eyes, ears, skeletal muscles, and heart. The mitochondrial DNA (mtDNA) rearrangements, especiall...

Mammalian sensory hair cells (HCs) have limited capacity for regeneration, which leads to permanent hearing loss after HC death. Here, we used in vitro RNA-sequencing to show that the Hippo signaling pathway is involved in HC damage and self-repair processes. Turning off Hippo signaling through Mst1/2 inhibition or Yap overexpression induces YAP nuclear accumulation, especially in supporting cells, which induces supernumerary HC production and HC regeneration after injury. Mechanistically, these effects of Hippo signaling work synergistically with the Notch pathway. Importantly, the supernumerary HCs not only express HC markers, but also have cilia structures that are able to form neural connections to auditory regions in vivo. Taken together, regulating Hippo suggests new strategies for promoting cochlear supporting cell proliferation, HC regeneration, and reconnection with neurons in mammals.

Hearing loss is the most common sensory neural disorder in human, and according to WHO estimation, 5.5% (466 million) people worldwide have disabling hearing loss. In this study, a Chinese family with prelingual sensorineural hearing loss was investigated. The affected individuals showed moderately-severe hearing loss at all frequencies. Using target genome enrichment and high-throughput sequencing, a homozygous mutation c.2372delC, p.S791Ffs*17 was identified in PDZD7. The deletion mutation lies in exon 15 of PDZD7 and resultes in a frame shift followed by an early stop codon. Our study expand the mutation spectrum of PDZD7 and strengthens the clinical importance of this gene in patients with moderately-severe hearing loss.

The urban green space (UGS) is essential for characterizing urban spatial configurations, ecological properties and environmental conservation. Thus, the urban green space is fundamental to urban planning management and renewal. UGS is mainly composed of park green areas, which are the public service facility providing people with outdoor activity spaces, so that UGS has a great impact on the protection of residents’ mental and physical health. Therefore, the reasonable layout of urban green space is of great significance. In this study, we took central area of Chongqing City as an example to study the accessibility of urban green spaces using very-high-resolution (VHR) remote sensing images by the network analysis model. The result showed that (1) both the spatial distribution information of urban green spaces and road network can be presented to provide urban-function information using VHR; (2)the accessible service area of urban green spaces in the study area accounted for 27.80% within 45 minutes;(3) and the equity of accessibility of UGS in Yuzhong District was the best.The accessibility analysis of urban green spaces is the basis of sustainable urban Planning.

Urban green space (UGS), as public services facilities that provide lots of outdoor space for people’s activities and exercise, has a significant impact on urban residents' social, psychological, and physical benefits. The reasonable distribution of the urban green space is of great significance for enhancing the overall well-being of urban dwellers. In this study, we selected Wuhan City center as a research area, extracted the spatial distribution information of urban green space, roads networks from high-resolution remote sensing images in 2019. The urban green space service situation in different travel modes, travel times, and parks types are subsequently calculated with a network analysis model in GIS. The results showed that the services area of urban green space in the city center of Wuhan was within a driving distance of 30 min, accounting for 70.38% of the total study area, and the use of high-resolution remote images spatial data can measure equity on a more precise scale.

Context The Sanjiangyuan region of the Qinghai-Tibetan Plateau—also known as the “Three Rivers’ Headwaters”—is the origin of the Yellow, Yangtze, and Mekong Rivers and therefore the key water source for hundreds of millions of downstream residents. Protecting this region’s ecosystems is a key priority for sustainable development in China and Asia. An important social dimension of Sanjiangyuan is the long-established and widespread presence of Tibetan Buddhism, particularly as manifested in the large number of monasteries throughout the region. However, the influence of cultural factors on environmental change remains largely understudied here. Objective We focus on two types of spatial associations—point-point and point-area features—to quantitatively investigate the effects of Buddhist monasteries on land use/cover change (LUCC) in surrounding landscapes. Methods We conduct a spatially-explicit analysis of Sanjiangyuan for two periods, 1990–2000 and 2010–2015, to identify and quantify the influence of the presence and spatial distributions of Buddhist monasteries on LUCC compared to village communities that lack monasteries. Results We found that the presence of monasteries is highly correlated with the preservation of natural ecosystems, specifically of grasslands and forests. Within monastery buffer zones with radii between 1 and 10 km, 7.13–9.30% more grassland area and 7.14–7.47% more forest area remained around monasteries compared to villages. This contrast decreased with increasing distance to the monastery/village. Overall, built-up areas were also much smaller around monasteries than around villages, while unused land was more commonly transformed to forests and grasslands around monasteries. Conclusions These findings strongly support the idea that Buddhist culture, as manifested through its physical institutions and communities, are instrumental in achieving desired landscape conservation outcomes.

Myosin VI is an actin-associated molecular motor vital for auditory and vestibular function. It is encoded by MYO6 located on chromosome 6q13 in human. Pathogenic variants in MYO6 have been associated with both dominant and recessive forms of hearing loss. However, the molecular mechanisms remain unclear. We established a humanized knock-in mouse model, Myo6-C442Y, to mimic the p.C442Y missense variant identified in human patients with autosomal dominant nonsyndromic hearing loss designated as DFNA22. We characterized hearing and inner ear morphologies of Myo6-C442Y and wild-type control mice. We found that both homozygous and heterozygous Myo6-C442Y mice exhibited hearing loss from three weeks after birth that rapidly progressed to profound deafness by six to nine weeks of age. The hearing loss corresponded to the degeneration of hair cells in the organ of Corti. We also observed disorganized stereocilia with irregular morphological features by immunohistochemistry and scanning electron microscopy. Additionally, hearing loss and inner-ear morphological anomalies were more pronounced and deteriorated more drastically in homozygous than in heterozygous Myo6-C442Y mice, indicating a semi-dominant inheritance pattern. Heterozygous Myo6-C442Y mice recapitulated the progressive postlingual sensorineural deafness in human, thus providing a useful model for elucidating the role myosin VI plays in the mammalian auditory system. Furthermore, the late-onset hearing loss of this mouse model may provide a therapeutic window for the emerging gene therapy, a promising strategy to treat certain forms of genetic deafness.

Background Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. Results The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. Conclusions These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

Sensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and β-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or β-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea.

The Green-for-Grain program (GGP) is the largest environmental restoration program in China. It is effective in controlling land desertification but at the same time is highly affected by regional differences. Ecosystem health, as an important indicator of ecosystem sustainability, can effectively assess the ecological impact of the GGP and provide a basis for follow-up actions. As a typical agro-pastoral ecotone along the Great Wall, the Xilin Gol League has seen increasing land-use intensity, thus, it is crucial to understand the ecological conditions of the region in order to deploy a policy of the GGP in accordance with local conditions. In this study, using remote sensing images and social statistics data from 1990–2015, land-use transformation and the turning point of vegetation coverage was determined. Based on the pressure-state-response (PSR) model, an ecological health evaluation system was constructed to quantify the temporal and spatial variation of ecosystem health. Then, the spatial correlation between the changes in forest and grass coverage, as well as the changes in the ecosystem health index (EHI), was evaluated using GeoDa software. The results showed that (1) grassland was the primary land-use/land-cover (LULC) in the Xilin Gol League. Since 2000, land-use transfer types changed significantly and grassland degradation weakened; landscape connectivity increased, and vegetation coverage increased. (2) Over the past 25 years, the ecosystem in the study area was at a subhealthy level and showed a trend toward a healthy level. (3) The spatial correlation between △Area% (change in forest and grass coverage) and △EHI (change in ecosystem health index) was positive between 2000 and 2015 and the correlation gradually increased, indicating that the GGP did enhance the health of the ecosystem of Xilin Gol. This study provided a specific reference for the evaluation of ecosystem health in the agro-pastoral ecotone of China and a theoretical basis for the implementation of sustainable management policies in the study area.

Goal 15 of the UN Sustainable Development Goals (SDGs) has highlighted the importance of maintaining a sustainable relation between ecosystem services and human activities. Ecosystem services are heterogeneous across landscapes. However, how human activities, which cause disturbances to ecosystem services, relate to such heterogeneity has not been well studied and thus necessarily constraining our ability to manage ecosystems sustainably. Based on land use/land cover data, this study addressed the research gap by running two inter-related analyses on the datasets of the study area, i.e., Chuandong, China. The first analysis involves identifying distinctive heterogeneous units of ecosystem service values using Getis-Ord Gi⁎. The second analysis involves measuring the impacts of human disturbances on ecosystem service values and their variations over every five years between 1990 and 2015, using linear regression and spatial regression models. The result of the first analysis identified heterogeneous ecosystem service units of hot-spots, cold-spots, and random areas. The hot-spots mainly clustered in relative inaccessibility land at higher terrain gradients in the east of the study area. The cold-spots overlapped extensively with built-up areas and farmland at lower terrain gradients in the west of the study area. Random areas distributed mainly in the middle part of the study area. This heterogeneity also existed temporally. Ecosystem service values in the study area decreased from 1990 to 2000 but reversed the trend after 2000. The result of the second analysis revealed that the impacts of hot-spots, cold-spots, and random areas on the relationship between ecosystem service values and human disturbances vary. Specifically, there was a negatively linear relationship between ecosystem service values and the integrated indicator of human disturbances, which was the strongest in random areas, followed by cold-spots and hot-spots. In addition, spatial spillover effect is explicit in the relationship between ecosystem service values and three specific factors of human disturbances, i.e., terrain index, population, and gross domestic product. They varied significantly between units: the terrain index had a positive externality on ecosystem service values with cold-spots and random areas but negative externality with hot-spots; population imposed a more negative externality on ecosystem service values when in proximity to random areas than cold-spots and hot-spots; the externality between gross domestic product and ecosystem service values exhibited irregular inverse 'U' shape, which was below the 'X-axis' in cold-spots but throughout the 'X-axis' in hot-spots and random areas. The findings of this study have potential policy implications in improving ecosystem sustainability through harmonizing the environment and human activities.

The Three Rivers Headwaters Region is one of the most import ecological protection regions and Tibetan inhabited regions in China. Located in the Qinghai province of China, the Region is the source of the Yangtze, the Yellow and the Lantsang-Mekong Rivers. This study region was based on remote sensing imagery. An ecological landscape classification of the area is presented, as well as a suite of landscape indices for landscape pattern changes from 1987 to 2015. The influence of human activities on the landscape change of study area is discussed. The results showed landscape structure complexity, fragmentation gradually increased, while the indices of contagion and evenness were decreased. Structure characteristic of landscape change in this region are more obvious, especially, the difference in space distributions of part and the whole. There were trend of uniform distribution of different types and diversity gradually increased in the source of Yangtze River. And an opposite tendency is showing in the Yellow River and Lantsang-Mekong River. Physical-geographical conditions, climate change and government policy at study period were the main reasons of significant landscape pattern change. This study proposes management measures for sustainable development in the Three Rivers Headwaters Region.

A total of 200 smoking-related laryngeal carcinoma patients with pathology confirmation from the Eye and ENT Hospital and 190 high-risk smokers were included in a survey. All of the participants had a smoking index greater than 400 (cigarettes/day*year.) We obtained data on clinical and baseline characteristics, and peripheral blood was obtained and subjected to DNA extraction to analyse the correlation between smoking and the occurrence of laryngeal carcinoma. We selected candidate genes and SNP fragments that were found to be closely associated with smoking-related tumours in preliminary studies. The selected candidate genes were XPG, CYP1A1, OGG1, ERCC5, ERCC1, MMP2, and MMP9. We then performed SNP sequencing using Sequenom SNP detection technology. Target genes and single nucleotide polymorphism (SNP) fragments were evaluated to analyse the correlation between genotype or allele and smoking-related laryngeal carcinoma and to identify susceptibility genes related to laryngeal carcinoma. The results included four main findings: (1) The smoking index differed significantly between laryngeal cancer patients and control subjects (P=0.0035). The risk of laryngeal cancer was increased among individuals with a smoking index greater than 600 cigarettes/day*year (P=0.03). (2) The smoking index was significantly correlated with the T, N and clinical stages (P

Rapid expansions of urban areas and the intensification of human activities have severely impacted ecosystems and ecosystem service provisions. Considering limited availability of ecosystem services, the evaluation of ecosystem service value should consider its fluctuations supply and demand due to urbanization, i.e., the ecosystem service scarcity value (ESSV). Taking typical arid and semiarid regions of China and the Ningxia Hui Autonomous Region as an example, the effects of different scarcity factors on the scarcity value of ecosystem services were compared. At the same time, a geographically weighted regression model (GWR) was developed to analyze the spatial relationships between urbanization and the scarcity value of ecosystem services. The results suggest that demand-driven scarcity is the most important factor affecting the ESSV in Ningxia, and between 1990 and 2015, the ESSV in Ningxia increased significantly, with increase being more evident from 2005 to 2015. Among the different types of ecosystem services, the scarcity values of ecosystem services such as air quality, waste treatment, soil retention, biodiversity services, and recreation and culture increased significantly from 1990 to 2015. Spatially, the total ESSV and the ESSV of different ecosystem service types exhibited evident spatial heterogeneity due, to spatial distribution characteristics of land-use type, population density and per capita GDP. The GWR modeling result shows, that the impact of urbanization on ESSV was positively correlated overall. The ESSV of food production, raw material, air quality, climate regulation and water supply are greatly affected by urbanization, while the ESSV of biodiversity services and recreation and culture are less affected by urbanization. Meanwhile, the High-Low type and Low-High type had significant aggregation effects in the study area.

In the process of rapid urbanization, the decline in ecosystems' physical supply value is a direct result of the increasing demands of human development. The ecosystem services value combined with supply and demand factors can be used to obtain the ecosystem services scarcity value (ESSV). These ecosystems with larger ESSVs warrant increased protection, or at the very least a development plan to ensure a balance between their continued existence and human usage. However, urbanization and other developmental effects have often caused the ESSV of those regions to be disregarded, which produces an imbalance in the ecosystem. This paper evaluated the spatial differentiation of ESSV based on heterogeneous units in the Yuebei region, China. Then, a spatial response analysis of the ESSV to urbanization according to the spatial correlation model and Getis-Ord Gi* was conducted. The results showed that the ecosystem service physical supply value declined due to urban sprawl in 1990–2015, but the ESSV increased sharply during the same time with its acceleration being particularly strong after 2000. Areas with higher ESSV were concentrated in the northern region due to a higher prevalence of woodland. Urbanization accelerated significantly after 2000, and it is found that similar tendencies of ESSV and urbanization occurred over the same period. Surprisingly, the ESSV was negatively correlated with urbanization in local regions, and their interaction continued to increase over time. The spatial hotspot map of the ESSV and urbanization also formed an opposite pattern. In addition, the grid number of High-Low and Low-High types is more than half of the total number of aggregated grids. According to the results, understanding the variation in the ESSV clearly due to urbanization and identifying their interaction in local regions can provide a more specific direction for future resource adjustment and ecosystem service improvements.

Treacher Collins syndrome (TCS) (OMIM 154500) is a rare congenital craniofacial disorder with an autosomal dominant manner of inheritance in most cases. To date, three pathogenic genes (TCOF1, POLR1D and POLR1C) have been identified. In this study, we conducted mutational analysis on Chinese TCS patients to reveal a mutational spectrum of known causative genes and show phenotype-genotype data to provide more information for gene counselling and future studies on the pathogenesis of TCS. Twenty-two TCS patients were recruited from two tertiary referral centres, and Sanger sequencing for the coding exons and exon-intron boundaries of TCOF1, POLR1D and POLR1C was performed. For patients without small variants, further copy number variations (CNVs) analysis was conducted using high-density SNP array platforms. The Sanger sequencing overall mutation detection rate was as high as 86.3% (19/22) for our cohort. Fifteen TCOF1 pathogenic variants, including ten novel mutations, were identified in nineteen patients. No causative mutations in POLR1D and POLR1C genes and no CNVs mutations were detected. A suspected autosomal dominant inheritance case that implies germinal mosaicism was described. Our study confirmed that TCOF1 was the main disease-causing gene for the Chinese TCS population and revealed its mutation spectrum. We also addressed the need for more studies of mosaicism in TCS cases, which could explain the mechanism of autosomal dominant inheritance in TCS cases and benefit the prevention of TCS.

The unprecedented rate of urbanization in China since 1978 has profoundly impacted its landscape and threatened ecosystem sustainability. To devise effective sustainable development policy, it is imperative to quantify the relationships between urbanization and ecosystem services in a spatially explicit manner. For this purpose, ecosystem service value (ESV) is commonly adopted, especially, in evaluating the changes of ecosystem services in terms of physical supply capacities. Existing research efforts, however, rarely considered the scarcity caused by the supply-demand dynamics, which was incorporated into ESV, or succinctly, ecosystem service scarcity value (ESSV). In addition, they tended to focus on the local and regional levels, leaving unattended the national level analysis that carries important policy implications. This paper fills this gap by quantifying first the spatiotemporal patterns of ESSV and their changes at the province level for China, and second the spatial variations of the relationship between urbanization and ecosystem services employing geographically weighted regression (GWR) model. The results showed that the ESSV was highest in the southeast and lowest in the northwest in China and the total ESSV in all provinces trended upward from 1990 to 2015. The population growth, urban land expansion, and economic growth due to urbanization were clearly higher in the eastern coastal areas and the areas along the Yangtze River than in other regions. The ESSV and gross domestic product growth of developed regions both shared the same growth trend over time; in particular developed regions saw a sharper increase than less developed regions. This showed a positive correlation between the ESSV of a region and its economic situation. The changes of spatial impacts of urbanization on ESSV were mainly driven by regional development policy, which was confirmed by the results from GWR. Therefore, promoting a holistic view of land use functions with socioeconomic activities, such as maintaining a balanced urban development, implementing ecological compensation and strengthening regional cooperation across administrative boundaries, is encouraged to reconcile the conflict between urbanization and ecosystem management.

MnO2-decorated magnesium wire composite (MnO2-M) was fabricated via a simple hydrothermal reaction and accompanied by the calcination process (MnO2/Mn3O4-M). To clarify the optimized reaction condition of δ-MnO2 in the system, the effect of different pH, temperature and pollutant concentration of methyl orange (MO) for degradation process were investigated. Experimental results showed that MnO2-M achieves a high removal rate of 76% (2h, at 25°C) in the presence of H2O2 at pH 2.5, which is higher than that of MnO2/Mn3O4-M (54%). Moreover, reaction temperature and MO dye concentration have little effect on the degradation performance of MnO2-M. This implies the stability of the as-prepared samples and good potential in the application of wastewater treatment.

Evaluating the impact of an ecological restoration program on ecosystem services is crucial, given the role of such a program in boosting sustainable ecosystem management. This study examines the impact of one of the large-scale ecological restoration programs in China, the Grain for Green Program (GGP), on ecosystem service management in the Exibei region of China. This region is studied, as it is a key source water area with rich biodiversity and has been experiencing GGP for 20 years. To achieve the stated goal the changes of land use and ecosystem services value (ESV) and the ecosystem services scarcity value (ESSV) in the Exibei region were quantified and assessed based on remote sensing images from 1990, 1995, 2000, 2005, 2010, 2015 and field survey data. The results indicated that the expansion of construction land and the increase of water body were the dominant land use changes throughout the study period. Farmland, forestland and grassland decreased by 2.61%, 0.47% and 1.41% after the GGP, respectively. The ESV of the entire Exibei region increased slightly in response to land use change during 1990&ndash, 2015, with an annual loss of 0.08% before the implementation of GGP and an annual growth of 0.03% after the implementation of GGP. Moreover, forestland was the dominant contributor to ESSV after the implementation of the GGP. Its annual growth rate was four times higher than before the commencement of GGP. The results of this study contribute to the protection of the Exibei region ecosystem, and more importantly, the future management of the ecosystem service in the hilly regions of southern China.

It is estimated that at least 50% of congenital or childhood hearing loss is attributable to genetic causes. In non-syndromic hearing loss, which accounts for 70% of genetic hearing loss, approximately 80% of cases are autosomal recessive, 15% autosomal dominant, and 1-2% mitochondrial or X-linked. In addition, 30% of genetic hearing loss is syndromic. The genetic causes of hearing loss are highly heterogeneous. So far, more than 140 deafness-related genes have been discovered. Studies on those genes tremendously increased our understanding of the inner ear functions at the molecular level. It also offers important information for the patients and allows personalized and accurate genetic counseling. In many cases, genetic diagnosis of hearing loss can help to avoid unnecessary and costly clinical testing, offer prognostic information, and guide future medical management. On the other hand, a variety of gene therapeutic approaches have been developed aiming to relieve or converse the hearing loss due to genetic causes. Prevention of genetic hearing loss is feasible through prepregnancy and prenatal genetic diagnosis and counseling.

It is estimated that at least 50% of congenital or childhood hearing loss is attributable to genetic causes. In non-syndromic hearing loss, which accounts for 70% of genetic hearing loss, approximately 80% of cases are autosomal recessive, 15% autosomal dominant, and 1–2% mitochondrial or X-linked. In addition, 30% of genetic hearing loss is syndromic. The genetic causes of hearing loss are highly heterogeneous. So far, more than 140 deafness-related genes have been discovered. Studies on those genes tremendously increased our understanding of the inner ear functions at the molecular level. It also offers important information for the patients and allows personalized and accurate genetic counseling. In many cases, genetic diagnosis of hearing loss can help to avoid unnecessary and costly clinical testing, offer prognostic information, and guide future medical management. On the other hand, a variety of gene therapeutic approaches have been developed aiming to relieve or converse the hearing loss due to genetic causes. Prevention of genetic hearing loss is feasible through prepregnancy and prenatal genetic diagnosis and counseling.

The generation of hair cells (HCs) from the differentiation of proliferating supporting cells (SCs) appears to be an ideal approach for replacing lost HCs in the cochlea and is promising for restoring hearing after damage to the organ of Corti. We show here that extensive proliferation of SCs followed by mitotic HC generation is achieved through a genetic reprogramming process involving the activation of β-catenin to upregulate Wnt signaling, the deletion of Notch1 to downregulate Notch signaling, and the overexpression of Atoh1 in Sox2(+) SCs in neonatal mouse cochleae. We used RNA sequencing to compare the transcripts of the cochleae from control mice and from mice with β-catenin activation, Notch1 deletion, and β-catenin activation combined with Notch1 deletion in Sox2(+) SCs. We identified the genes involved in the proliferation and transdifferentiation process that are either controlled by individual signaling pathways or by the combination of Wnt and Notch signaling. Moreover, the proliferation of SCs induced by Notch1 deletion disappears after deleting β-catenin in Notch1 knock-out Sox2(+) cells, which further demonstrates that Notch signaling is an upstream and negative regulator of Wnt signaling. SIGNIFICANCE STATEMENT We show here that the extensive proliferation of supporting cells (SCs) and the subsequent mitotic hair cell (HC) generation is achieved through a genetic reprogramming process involving activation of β-catenin to upregulate Wnt signaling, deletion of Notch1 to downregulate Notch signaling, and overexpression of Atoh1 in Sox2(+) SCs in neonatal mice cochleae. By comparing the transcripts of the cochleae among controls, β-catenin activation, Notch1 deletion, and β-catenin activation combined with Notch1 deletion group, we identified multiple genes involved in the proliferation and transdifferentiation process that are either controlled by individual signaling pathways or by the combination of Wnt and Notch signaling. This provides a better understanding of the mechanisms behind mitotic HC generation and might provide new approaches to stimulating mitotic HC regeneration.