Urban-rural disparities in the association of nitrogen dioxide exposure with cardiovascular disease risk in China: effect size and economic burden.

BACKGROUND: Together with rapid urbanization, ambient nitrogen dioxide (NO2) exposure has become a growing health threat. However, little is known about the urban-rural disparities in the health implications of short-term NO2 exposure. This study aimed to compare the association between short-term NO2 exposure and hospitalization for cardiovascular disease (CVD) among urban and rural residents in Shandong Province, China. Then, this study further explored the urban-rural disparities in the economic burden attributed to NO2 and the explanation for the disparities. METHODS: Daily hospitalization data were obtained from an electronic medical records dataset covering a population of 5 million. In total, 303,217 hospital admissions for CVD were analyzed. A three-stage time-series analytic approach was used to estimate the county-level association and the attributed economic burden. RESULTS: For every 10-µg/m3 increase in NO2 concentrations, this study observed a significant percentage increase in hospital admissions on the day of exposure of 1.42% (95% CI 0.92 to 1.92%) for CVD. The effect size was slightly higher in urban areas, while the urban-rural difference was not significant. However, a more pronounced displacement phenomenon was found in rural areas, and the economic burden attributed to NO2 was significantly higher in urban areas. At an annual average NO2 concentration of 10 µg/m3, total hospital days and expenses in urban areas were reduced by 81,801 (44,831 to 118,191) days and 60,121 (33,002 to 86,729) thousand CNY, respectively, almost twice as much as in rural areas. Due to disadvantages in socioeconomic status and medical resources, despite similar air pollution levels in the urban and rural areas of our sample sites, the rural population tended to spend less on hospitalization services. CONCLUSIONS: Short-term exposure to ambient NO2 could lead to considerable health impacts in either urban or rural areas of Shandong Province, China. Moreover, urban-rural differences in socioeconomic status and medical resources contributed to the urban-rural disparities in the economic burden attributed to NO2 exposure. The health implications of NO2 exposure are a social problem in addition to an environmental problem. Thus, this study suggests a coordinated intervention system that targets environmental and social inequality factors simultaneously.

Research on oxygen enrichment for municipal solid waste fly ash melting: A pilot-scale study on natural gas and coal as the melting fuel.

High energy consumption is the main obstacle of melting/vitrification technology for the disposal of municipal solid waste incineration fly ash (MSWIFA) for industrial applications. To reduce energy consumption and lower operating costs, oxygen enrichment melting was proposed and studied in this work. This research was conducted in a pilot-scale melting furnace, and three melting conditions were compared and discussed. The results showed that 66% of natural gas was saved and the operating cost was reduced by 55% when oxygen enrichment technology was applied to MSWIFA melting. When coal was used as the fuel with the oxygen enrichment melting technology, the operating cost was even lower at 66.39 dollar/ton of fly ash. Because MSWIFA was a Ca-rich material, the relatively high content of Si and Al in the coal fly ash promoted the formation of vitrificated slag, leading to a reduction in the overall pollution toxicity index (OPTI) of MSWIFA by 99.98%. Meanwhile, SO2, HCl, and secondary fly ash were the main pollutants during MSWIFA melting, and when coal was used as the fuel, the emissions of SO2 and HCl could be reduced and the OPTI of secondary fly ash was suppressed. These results suggested that to obtain the lowest operating cost and reduce secondary pollution during MSWIFA melting, the best option consisted of oxygen enrichment technology with coal as the fuel.

Early onset atrial lesions in a patient with a novel LMNA frameshift mutation.

Genetic mutations in the lamin A/C gene (LMNA) have been linked to cardiomyopathy. Different mutational sites exhibit different clinical manifestations and prognoses. Herein, we identified a novel LMNA frameshift mutation, p.P485Tfs*67, from a patient with early-onset atrial disease. To verify the pathogenicity of this variation, a transgenic zebrafish model was constructed, which demonstrated that adult zebrafish with the LMNA mutation showed an abnormal ECG and impaired myocardial structure. Our study suggests the atrial pathogenicity of the LMNA-P485Tfs mutation, which is helpful to understand the function of the Ig-like domain of lamin A/C.

Improving the Enantioselectivity of CHMOBrevi1 for Asymmetric Synthesis of Podophyllotoxin Precursor.

(R)-ß-piperonyl-γ-butyrolactones are key building blocks for the synthesis of podophyllotoxin, which have demonstrated remarkable potential in cancer treatment. Baeyer-Villiger monooxygenases (BVMOs)-mediated asymmetric oxidation is a green approach to produce chiral lactones. While several BVMOs were able to oxidize the corresponding cyclobutanone, most BVMOs gave the (S) enantiomer while Cyclohexanone monooxygenase (CHMO) from Brevibacterium sp. HCU1 gave (R) enantiomer, but with a low enantioselectivity (75 % ee). In this study, we use a strategy called "focused rational iterative site-specific mutagenesis" (FRISM) at residues ranging from 6 Šfrom substrate. The mutations by using a restricted set of rationally chosen amino acids allow the formation of a small mutant library. By generating and screening less than 60 variants, we achieved a high ee of 96.8 %. Coupled with the cofactor regeneration system, 9.3 mM substrate was converted completely in a 100-mL scale reaction. Therefore, our work reveals a promising synthetic method for (R)-ß-piperonyl-γ-butyrolactone with the highest enantioselectivity, and provides a new opportunity for the chem-enzymatic synthesis of podophyllotoxin.

Hepatitis E virus-encoded microRNA promotes viral replication by inhibiting type I interferon.

MicroRNAs (miRNAs), the non-coding RNAs of ~22 nucleotides (nt) in length, play a vital role in regulating viral replication. Hepatitis E virus (HEV), a single-stranded RNA virus, is a predominant pathogen of acute hepatitis worldwide. Virus-encoded miRNAs regulate the viral life cycle and escape from the host innate immune system. However, it is rarely known about HEV-encoded miRNA (HEV-miR-A6). In the present study, HEV-miR-A6 was screened by microarray, and further identified in vivo and in vitro. HEV-miR-A6 originated from the methylase (MeT) of HEV open reading frame 1 (ORF1) and was highly conserved in eight HEV genotypes. HEV-miR-A6 expression was growing during HEV replication, and significantly increased in acute hepatitis E patients than convalescence patients. Furthermore, HEV-miR-A6 was specifically detected in liver, spleen, kidney and colon by in situ hybridization. To identify the specificity of HEV-miR-A6, its mutants (HEV-miR-A6M1 and HEV-miR-A6M2) were constructed to change the stem-loop structure. Interestingly, over-expression of HEV-miR-A6 or HEV-miR-A6M1 significantly facilitated viral replication, while HEV-miR-A6M2, another mutant completely changed the stem-loop structure was invalid. SIRP-α, a candidate target gene of HEV-miR-A6, was activated when HEV-miR-A6 over-expressed to inhibit the phosphorylation of IRF3, and subsequently suppressed the expression of type I interferon ß (IFN-ß). The promotion of viral replication by HEV-miR-A6 further identified in vivo. Significant suppression of IFN-ß production in the serum of HEV-infected mice pre-treated with HEV-miR-A6 was observed. In summary, HEV-miR-A6 activates SIRP-α to promote viral replication by inhibition of IFN-ß expression.

Severe maternal-fetal pathological damage and inflammatory responses contribute to miscarriage caused by hepatitis E viral infection during pregnancy.

BACKGROUND: Hepatitis E virus (HEV) infection causes serious adverse pregnancy outcomes during pregnancy. However, the maternal and fetal damage induced by HEV infection is rarely reported. METHODS: A BALB/c pregnant mouse model was established to explore the maternal and fetal pathological damage and inflammatory responses caused by HEV infection. RESULTS: Notably, miscarriages and stillbirths were observed in HEV-infected pregnant mice. HEV infections were identified by qRT-PCR, immunohistochemical analysis and immunofluorescence assay in the uterus, placenta, umbilical cords and livers and brains of fetuses. Serious inflammatory responses and pathological damage were triggered in the uterus and placenta of HEV-infected pregnant mice. Vertical transmission of HEV resulted in severe pathological damage and inflammatory responses in the livers and brains of fetuses, as well as emerging apoptosis cells in the brains of fetuses. Most of the cytokines/chemokines in the sera were significantly increased in the HEV-infected pregnant mice. Remarkably, cytokines/chemokines were significantly different between HEV-infected pregnant and miscarriage mice; IL9, GM-CSF and IL1α were the most important three cytokines/chemokines in determining the pregnancy outcomes. CONCLUSION: HEV infections cause serious maternal/fetal pathological damage, inflammatory responses and apoptosis, which may be responsible for adverse pregnancy outcomes.

The Objective Dementia Severity Scale Based on MRI with Contrastive Learning: A Whole Brain Neuroimaging Perspective.

In the clinical treatment of Alzheimer's disease, one of the most important tasks is evaluating its severity for diagnosis and therapy. However, traditional testing methods are deficient, such as their susceptibility to subjective factors, incomplete evaluation, low accuracy, or insufficient granularity, resulting in unreliable evaluation scores. To address these issues, we propose an objective dementia severity scale based on MRI (ODSS-MRI) using contrastive learning to automatically evaluate the neurological function of patients. The approach utilizes a deep learning framework and a contrastive learning strategy to mine relevant information from structural magnetic resonance images to obtain the patient's neurological function level score. Given that the model is driven by the patient's whole brain imaging data, but without any possible biased manual intervention or instruction from the physician or patient, it provides a comprehensive and objective evaluation of the patient's neurological function. We conducted experiments on the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset, and the results showed that the proposed ODSS-MRI was correlated with the stages of AD 88.55% better than all existing methods. This demonstrates its efficacy to describe the neurological function changes of patients during AD progression. It also outperformed traditional psychiatric rating scales in discriminating different stages of AD, which is indicative of its superiority for neurological function evaluation.

Image-restoration algorithm based on an underwater polarization imaging visualization model.

The polarization bidirectional reflection distribution function theory of a target is combined with microfacet theory, and the Monte Carlo method is used to establish an underwater laser active-polarization imaging model based on Mie scattering theory. The model presented herein can simulate imaging of an underwater target with a high degree of polarization, and the effects of optical thickness and target surface roughness on active underwater laser imaging results are demonstrated by the simulation image. Combined with histogram equalization and the traditional polarization differential imaging algorithm, an algorithm is presented herein that globally estimates the mutual information value between the target polarization degree and the correction factor of backscattered light polarization degree. The images received from the simulation test can be restored, and results show that the algorithm can restore the target image with a high degree of polarization to some extent. Finally, the correctness of the active underwater laser polarization imaging model and the feasibility of global estimation based on the polarization differential restoration algorithm are verified experimentally.

The different replication between nonenveloped and quasi-enveloped hepatitis E virus.

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. However, the understanding of the HEV life cycle is limited. In the present study, cells were separately infected with nonenveloped HEV (derived from feces or bile) or quasi-enveloped HEV (derived from the cell culture after serial passages, eHEV) and observed by confocal fluorescence microscopy to investigate the life cycle of HEV. HEV finished its binding and entry into host cells at first 6 h postinoculation (hpi). Cells inoculated with eHEV showed less infectivity than cells inoculated with nonenveloped HEV. Newly synthesized progeny virions were released into the supernatant of cell cultures from 48 hpi. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis results showed that the supernatant's progeny viruses were infectious even after five serial passages. These results show the significant difference between nonenveloped HEV and eHEV, which will provide novel insights into the HEV replication cycle. The efficient cell culture of HEV will promote the development of anti-HEV drugs and vaccines.

Hepatitis E viral infection regulates estrogen signaling pathways: Inhibition of the cAMPK-PKA-CREB and PI3K-AKT-mTOR signaling pathways.

Hepatitis E virus (HEV) infection has become a global concern with high mortality rates among pregnant women, especially those in their third trimester of pregnancy. Estrogen plays an important role in mediating the body, regulating physiological and pathological processes. Estrogen is activated by binding to estrogen receptors (ERs) and mediates rapid signaling events by pathways that involve transmembrane ERs. Our previous study had confirmed that high estrogen levels during pregnancy are associated with high HEV titers. However, the association between HEV infection and estrogen signaling pathways remains unclear. In the present study, the regulation of estrogen signaling pathways by HEV infection was evaluated. Results demonstrated that HEV infection significantly inhibits the cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways, but is independent of the Ras-Raf-MEK-ERK signaling pathway. In summary, the increasing estrogen levels and highly activated ERα during pregnancy aggravates HEV replication. The exacerbation of HEV replication, in turn, inhibits ERα expression and suppresses both cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways.

Spatially Resolved Electric-Field Manipulation of Magnetism for CoFeB Mesoscopic Discs on Ferroelectrics.

Electric-field control of magnetism in ferromagnetic/ferroelectric multiferroic heterostructures is a promising way to realize fast and nonvolatile random-access memory with high density and low-power consumption. An important issue that has not been solved is the magnetic responses to different types of ferroelectric-domain switching. Here, for the first time three types of magnetic responses are reported induced by different types of ferroelectric domain switching with in situ electric fields in the CoFeB mesoscopic discs grown on PMN-PT(001), including type I and type II attributed to 109°, 71°/180° ferroelectric domain switching, respectively, and type III attributed to a combined behavior of multiferroelectric domain switching. Rotation of the magnetic easy axis by 90° induced by 109° ferroelectric domain switching is also found. In addition, the unique variations of effective magnetic anisotropy field with electric field are explained by the different ferroelectric domain switching paths. The spatially resolved study of electric-field control of magnetism on the mesoscale not only enhances the understanding of the distinct magnetic responses to different ferroelectric domain switching and sheds light on the path of ferroelectric domain switching, but is also important for the realization of low-power consumption and high-speed magnetic random-access memory utilizing these materials.

Identification and Expression Analysis of Polygalacturonase Family Members during Peach Fruit Softening.

Polygalacturonase (PG) is an important hydrolytic enzyme involved in pectin degradation during fruit softening. However, the roles of PG family members in fruit softening remain unclear. We identified 45 PpPG genes in the peach genome which are clustered into six subclasses. PpPGs consist of four to nine exons and three to eight introns, and the exon/intron structure is basically conserved in all but subclass E. Only 16 PpPG genes were expressed in ripening fruit, and their expression profiles were analyzed during storage in two peach cultivars with different softening characteristics. Eight PGs (PpPG1, -10, -12, -13, -15, -23, -21, and -22) in fast-softening "Qian Jian Bai" (QJB) fruit and three PGs (PpPG15, -21, and -22) in slow-softening "Qin Wang" (QW) fruit exhibited softening-associated patterns; which also were affected by ethylene treatment. Our results suggest that the different softening characters in QW and QJB fruit is related to the amount of PG members. While keeping relatively lower levels during QW fruit softening, the expression of six PGs (PpPG1, -10, -12, -11, -14, and -35) rapidly induced by ethylene. PpPG24, -25 and -38 may not be involved in softening of peach fruit.

Gender-specific association of the accumulation of chronic conditions and disability in activities of daily living with depressive symptoms.

BACKGROUND: In the era of rapid aging with a rising prevalence of multimorbidity, complex interactions between physical and psychological conditions have challenged the health care system. However, little is known about the association of the accumulation of chronic conditions and disability in activities of daily living with depressive symptoms, especially in developed countries. METHODS: This population-based cohort study used data from the Health and Retirement Study. A total of 22,335 middle-aged and older adults participated in the 2014 (T1), 2016 (T2), and 2018 (T3) waves of the cohort were included. The accumulation of chronic conditions and disability were defined as the number of chronic diseases and the five activities of daily living. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale. A longitudinal mediation model with a cross-lagged panel model was run. As robust check, the models were applied with a longer follow-up period (from 2012 to 2018). Additionally, results were estimated in China. RESULTS: Bidirectional associations have been found among the accumulation of chronic conditions, disability, and depressive symptoms, especially between disability and depression. Disability (T2) mediated 11.11 % and 16.87 % of the association between the accumulation of chronic conditions (T1) and depression (T3) for men and women in the United States. The results were consistent in robust analysis. CONCLUSIONS: This study found that men and women routinely experienced disability and depressive symptoms because of the accumulation of chronic conditions. In terms of depressive symptoms, women were more sensitive to the accumulation of chronic conditions through disability.

Inter- and intrapopulation differences in the association between physical multimorbidity and depressive symptoms.

BACKGROUND: The association between physical multimorbidity and depression differs by populations. However, no direct inter- or intrapopulation comparison of the association has been conducted. Thus, this study aims to estimate the association in China and the United States and reveal inter- and intrapopulation differences in the association. METHODS: Middle-aged and older adults from the China Health and Retirement Longitudinal Study and the Health and Retirement Study were included. Physical multimorbidity was defined as the simultaneous presence of two or more chronic physical conditions and depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale. Generalized estimating equation model and stratification multilevel method were the main statistical models. RESULTS: The presence of physical multimorbidity was associated with a higher risk of depression in both China (RR = 1.360 [95 % CI: 1.325-1.395]) and the US (RR = 1.613 [95 % CI: 1.529-1.701]). For individuals at a low risk of multimorbidity, multimorbidity was associated with 47.4 % (95 % CI: 1.377-1.579) and 71.1 % (95 % CI: 1.412-2.074) increases in the likelihood of depression in China and the US. The effect size was smaller for individuals at a moderate or high risk. However, the cross-national differences were greater for those with a high risk of multimorbidity. LIMITATIONS: The self-report measures, attribution bias. CONCLUSIONS: Compared to Chinese adults, the presence of physical multimorbidity led to an additional increase in depressive symptoms for American counterparts. The association was stronger for individuals at a low risk of multimorbidity, but cross-national differences were observed mostly among individuals at a high risk.

Key roles of insulin receptor InR1 in initiating reproductive diapause in males of the cabbage beetle Colaphellus bowringi (Coleoptera: Chrysomelidae).

BACKGROUND: Reproductive diapause serves as a valuable strategy enabling insects to survive unfavorable seasonal conditions. However, forcing insects into diapause when the environment is conducive to their well-being can cause them to miss out on seasonal opportunities for reproduction. This outcome not only reduces insect populations but also minimizes crop losses caused by insect feeding. Therefore, altering the timing of diapause initiation presents a potential strategy for managing pests. In this study, we examined the possible role of the Insulin Receptor 1 (InR1) in controlling reproductive diapause entry in the male cabbage beetle, Colaphellus bowringi. RESULTS: Compared to short-day (SD) conditions, long-day (LD) conditions led to reproductive diapause of C. bowringi males, characterized by arrested gonad development, increased Triglyceride (TG) accumulation, and upregulated expression of diapause protein 1 and genes associated with lipogenesis and stress tolerance. Upon employing RNA interference to knock down InR1 under SD conditions, males destined for reproduction were compelled into diapause, evidenced by arrested gonadal development, accumulation of TG, and elevated expression of diapause-related genes. Intriguingly, despite the common association of the absence of juvenile hormone (JH) with reproductive diapause in females, the knockdown of InR1 in males did not significant affect the expression of JH biosynthesis and JH response gene. CONCLUSION: The study highlight InR1 is a key factor involved in regulating male reproductive diapause in C. bowringi. Consequently, targeting insulin signaling could be a viable approach to perturb diapause timing, offering a promising strategy for managing pests with reproductive diapause capabilities. © 2024 Society of Chemical Industry.

Multifunctional Ultrathin Metasurface with a Low Radar Cross Section and Variable Infrared Emissivity.

The development of stealth devices that are compatible with both infrared (IR) and radar systems remains a significant challenge, as the material properties required for effective IR and radar stealth are often contradictory. In this work, based on an IR electrochromic device (IR-ECD), concepts of metamaterial manipulating electromagnetic waves are applied to develop a multifunctional ultrathin metasurface with a low radar cross section (RCS) and variable infrared emissivity. This paper presents a linear-to-linear polarization conversion metasurface (PCM) designed by hollowing the IR-ECD. In this way, the IR-ECD based on polyaniline (PANI) can also modulate the reflection waves in the microwave band without affecting its features in the infrared region. Thus, the proposed metasurface integrates both microwave stealth and variable infrared emissivity through a single layer. The measured results show that a 10 dB RCS reduction is achieved in the band of 8.46-9.5 GHz, and the infrared emissivity can be adjusted from 0.870 to 0.513 in the infrared stealth band of 8-14 µm. Due to the ultrathin thickness (only 0.081λ0 at 9 GHz), low RCS in the X-band, and variable infrared emissivity, the designed multifunctional stealth metasurface has promising applications on military platforms with various surrounding environments.

Injectable and Conductive Nanomicelle Hydrogel with α-Tocopherol Encapsulation for Enhanced Myocardial Infarction Repair.

Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.

Electric field control of perpendicular magnetic tunnel junctions with easy-cone magnetic anisotropic free layers.

Magnetic tunnel junctions (MTJs) are the core element of spintronic devices. Currently, the mainstream writing operation of MTJs is based on electric current with high energy dissipation, and it can be notably reduced if an electric field is used instead. In this regard, it is promising for electric field control of MTJ in the multiferroic heterostructure composed of MTJ and ferroelectrics via strain-mediated magnetoelectric coupling. However, there are only reports on MTJs with in-plane anisotropy so far. Here, we investigate electric field control of the resistance state of MgO-based perpendicular MTJs with easy-cone anisotropic free layers through strain-mediated magnetoelectric coupling in multiferroic heterostructures. A remarkable, nonvolatile, and reversible modulation of resistance at room temperature is demonstrated. Through local reciprocal space mapping under different electric fields for Pb(Mg1/3Nb2/3)0.7Ti0.3O3 beneath the MTJ pillar, the modulation mechanism is deduced. Our work represents a crucial step toward electric field control of spintronic devices with non-in-plane magnetic anisotropy.

Electric-field control of nonvolatile resistance state of perpendicular magnetic tunnel junction via magnetoelectric coupling.

Magnetic tunnel junctions (MTJs) are the core elements of spintronic devices. Now, the mainstream writing operation of MTJs mainly relies on electric current with high energy dissipation, which can be greatly reduced if an electric field is used instead. In this regard, strain-mediated multiferroic heterostructure composed of MTJ and ferroelectrics are promising with the advantages of room temperature and magnetic field-free as already demonstrated by MTJ with in-plane magnetic anisotropy. However, there is no such report on the perpendicular MTJs (p-MTJs), which have been commercialized. Here, we investigate electric-field control of resistance state of MgO-based p-MTJs in multiferroic heterostructures. A remarkable and nonvolatile manipulation of resistance is demonstrated at room temperature without magnetic field assistance. Through various characterizations and micromagnetic simulation, the manipulation mechanism is uncovered. Our work provides an effective avenue for manipulating p-MTJ resistance by electric fields and is notable for high density and ultralow power spintronic devices.

Novel WFS1 mutations in patients with low-to-middle frequency hearing loss.

BACKGROUND: Hearing loss (HL) is the most common sensorineural disorder in human. It is estimated that genetic factors contribute to over 50% of prelingual hearing loss. Most of dominant HHL patients manifest postlingual progressive hearing loss that mainly affect high frequencies. However, mutations in a few dominant HL genes, such as WFS1, TECTA and DIAPH1, cause distinct audiogram that primarily affects the low and middle frequencies. METHODS: We recruited twelve independent HL families with worse low or middle frequency audiograms. Each proband of these families was excluded for pathogenic mutations in GJB2, SLC26A4, and MT-RNR1 genes. Mutation screening was performed by whole exome sequencing. Next, candidate variants were validated in each family by sanger sequencing. RESULTS: Six heterozygous WFS1 variants were identified in six families, including three novel mutations (c.2519T > G, p.F840C; c.2048T > G, p.M683R and c.2419A > C, p.S807R) and three previously reported variants (c.2005T > C, p.Y669H; c.2590G > A, p.E864K and c.G2389A, p.D797 N). All the novel mutations were absent in 100 ethnically matched controls and were predicted to be deleterious by multiple algorithms. CONCLUSIONS: We identified three novel and three previously reported WFS1 mutations in six unrelated Chinese families. Our findings enriched the genotype-phenotype spectrum of WFS1 related NSHL. Additional genotype-phenotype correlation study will clarify the detailed phenotypic range caused by WFS1 mutations.