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Abstract Over 700 syndromes associated with hearing loss (HL) have been identified. Labyrinthine aplasia, microtia, and microdontia (LAMM syndrome, OMIM: 610706) is a rare HL syndrome characterized by congenital sensorineural HL, labyrinthine aplasia, type I microtia and microdontia, which is caused by biallelic variants in the FGF3 gene. Using Whole-exome sequencing (WES), we identified a novel missense FGF3 variant (c.137G > C, p. Arg46Pro (NM_005247.4) in three unrelated Uyghur ethnic families. This variant is classified as a variant of uncertain significance according to ACMG guidelines, with the applied criteria of PM3, PM2_Supporting, PP3 and PP4. Patients from the three families revealed variable clinical features. We found a novel phenotype, sparse hair, in one of the proband. Our findings expanded the variant and phenotype spectrum of LAMM syndrome and provided new insights to the diagnose and pathogenesis investigation of the disease.

Abstract DNA base editing technologies predominantly utilize engineered deaminases, limiting their ability to edit thymine and guanine directly. In this study, we successfully achieve base editing of both cytidine and thymine by leveraging the translesion DNA synthesis pathway through the engineering of uracil-DNA glycosylase (UNG). Employing structure-based rational design, exploration of homologous proteins, and mutation screening, we identify a Deinococcus radiodurans UNG mutant capable of effectively editing thymine. When fused with the nickase Cas9, the engineered DrUNG protein facilitates efficient thymine base editing at endogenous sites, achieving editing efficiencies up to 55% without enrichment and exhibiting minimal cellular toxicity. This thymine base editor (TBE) exhibits high editing specificity and significantly restores IDUA enzyme activity in cells derived from patients with Hurler syndrome. TBEs represent efficient, specific, and low-toxicity approaches to base editing with potential applications in treating relevant diseases.

BackgroundSeveral heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.MethodsPatients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.ResultsNinety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.ConclusionThe nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

BackgroundMore and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection.MethodsWe conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria.ResultsA total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [

Abstract 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.

Introduction: The unscented Kalman filter based on unbiased minimum-variance (UKF-UMV) estimation is usually used to handle the state estimation problem of nonlinear systems with an unknown input. When the nonlinear system is disturbed by non-Gaussian noise, the performance of UKF-UMV will seriously deteriorate.Methods: A maximum correntropy unscented filter based on the unbiased minimum variance (MCUF-UMV) estimation method is proposed on the basis of the UKF-UMV without the need for estimation of an unknown input and uses the maximum correntropy criterion (MCC) and fixed-point iterative algorithm for state estimation.Results: When the measurement noise of the nonlinear system is non-Gaussian noise, the algorithm performs well.Discussion: Our proposed algorithm also does not require estimation of an unknown input, and there is no prior knowledge available about the unknown input or any prior assumptions. The unknown input can be any signal. Finally, a simulation example is used to demonstrate the effectiveness and reliability of the algorithm.

Objective: To establish a preparation method of Atractylodes macrocephala Koidz polysaccharide (AMP) sulfate with anti-hyperplasia of mammary. Methods: AMP were sulfated by sulfated method, and the optimal conditions for the sulfated modification were determined by response surface methodology. The structures of AMP and SAMP were initially analyzed by infrared spectroscopy (IR) and High-Performance Gel Chromatography (HPGPC). The anti-oxidative activity in vitro of polysaccharide was investigated by testing the DPPH, ABTS+, OH free radical scavenging ability of AMP and SAMP. Rat model of mammary gland hyperplasia was established by intramuscular injection of estradiol benzoate and progesterone. The rats weight and breast diameter were recorded and the pathological organization form of mammary gland of rats were observed. Results: The optimum preparation conditions were as follows: Ratio of conditions of volume ratio of sulfuric acid and n-butanol 2:1, reaction temperature −4 ℃, reaction time 21 min. The degree of substitution of SAMP was 0.59±0.00391. The HPGPC results showed the relative molecular weights for AMP and SAMP were 2719 and 33524 Da, respectively. The IR spectra showed that SAMP had characteristic absorption peaks of S=O and C-O-S appeared near 833 and 1226 cm−1, indicating that the sulfated was successful. When the sample concentration was 0.5 mg/mL, the DPPH, ABTS+, OH free radical scavenging activities of SAMP were 54.91% , 38.21%, and 42.23%, respectively. Compared with the model group, the diameter of the nipples of the rats in the SAMP group decreased (P

Abstract Objective A rapid and accurate forecast for the early prognosis of ICH patients is challenging. This study investigated whether heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) could prognosticate poor neurological outcomes in ICH patients. Methods Between November 2020 and November 2021, we studied 92 spontaneous ICH patients in the First Affiliated Hospital of Nanjing Medical University. Glasgow Outcome Scale (GOS) score at 2 weeks after the ICH was used to categorize patients into good and poor outcome groups. The modified Rankin Scale (mRS) assessed patients' ability to live independently for 1 year. We utilized a portable high‐frequency electrocardiogram (ECG) recording system to record the HRV and SKNA information in ICH patients and control participants. Results 77 patients were eligible for the prediction of neurological outcome and were allocated into the good (n = 22) or poor (n = 55) outcome groups based on the GOS grade. In univariate logistic regression analysis, significant variables that could differentiate the outcomes were age, hypertension, tracheal intubation, Glasgow Coma Scale (GCS) score, existing intraventricular hemorrhage, white blood cells, neutrophil, lnVLF, lnTP, and aSKNA. Variables in the best fit multivariable logistic regression model were age, hypertension, GCS score, neutrophils, and aSKNA. The GCS score was the only independent risk factor for poor outcomes. At 30 days and 1 year of follow‐up, patients with lower aSKNA had poor outcomes. Interpretation ICH patients had reduced aSKNA, which could be a prognostic indicator. A lower aSKNA suggested a worse prognosis. The present data indicate that ECG signals could be helpful for prognosticating ICH patients.

Background: Cancer is a major health problem worldwide. A growing number of cancer patients travel to hospitals outside their residential cities due to unbalanced medical resources. We aimed to evaluate the association between patterns of patient mobility and survival among patients with cancer. Methods: Data of patients hospitalized for cancer between January 2015 and December 2017 were collected from the regional data platform of an eastern coastal province of China. According to the cities of hospitalization and residency, 3 mobility patterns including intra-city, local center, and national center pattern were defined. Patients with intra-city pattern were sequentially matched to patients with the other 2 patterns on demographics, marital status, cancer type, comorbidity, and hospitalization frequency, using propensity score matching. We estimated 5-year survival and the associations between all-cause mortality and patient mobility. Results: Among 20,602 cancer patients, there were 17,035 (82.7%) patients with intra-city pattern, 2,974 (14.4%) patients with local center pattern, and 593 (2.9%) patients with national center pattern. Compared to patients with intra-city pattern, higher survival rates were observed in patients with local center pattern [5-year survival rate, 69.3% versus 65.4%; hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.77 to 0.95] and in patients with national center pattern (5-year survival rate, 69.3% versus 64.5%; HR, 0.80; 95% CI, 0.67 to 0.97). Conclusions: We found significant survival disparities among different mobility patterns of patients with cancer. Improving the quality of cancer care is crucial, especially for cities with below-average healthcare resources.

Prioritizing areas and targets, coordinated with development gaps, is necessary to achieve the sustainable development goals (SDGs) in the face of resource limitations resulting from coronavirus disease 2019 (COVID-19). The SDG interlinkages further exacerbate the difficulty inherent in addressing these goals. However, previous studies failed to consider the indicator interlinkages in the process of aggregate performance assessments and thus cannot identify priorities based on indicator interlinkages and development gaps. This study integrated network analysis and the technique for order of preference by similarity to ideal solution (TOPSIS) method to convert indicator interlinkages into indicator weights and then assessed the aggregate performance of the SDGs. Subsequently, the prioritized provinces and indicators were identified at the subnational level of China based on the aggregate performance of the SDGs, SDG growth rate and indicator interlinkages. The per capita net income of rural residents (2.3.2), the proportion of people living below 50% of the median income (10.2.1), and the under-five mortality rate (3.2.1) were the most contributing indicators to the aggregate performance of the SDGs, while the common challenges dealt with SDG 16, SDG 6, SDG 7 and SDG 12. Moreover, accelerating the development of western provinces would make it possible to overcome the traditional imbalance status, while resource-driven provinces should be paid special attention due to their poor aggregate performance of the SDGs and their lower growth rate. Thus, a coordinating strategy is highly recommended for allocating resources to the priority targets and finally achieving the SDGs.

Background Individuals with asthma usually have comorbid sleep disturbances; however, whether sleep quality affects asthma risk is still unclear. We aimed to determine whether poor sleep patterns could increase the risk of asthma and whether healthy sleep patterns could mitigate the adverse effect of genetic susceptibility.Methods A large-scale prospective study was performed in the UK Biobank cohort involving 455 405 participants aged 38–73 years. Polygenic risk scores (PRSs) and comprehensive sleep scores, including five sleep traits, were constructed. A multivariable Cox proportional hazards regression model was used to investigate the independent and combined effects of sleep pattern and genetic susceptibility (PRS) on asthma incidence. Subgroup analysis across sex and sensitivity analysis, including a 5-year lag, different covariate adjustments and repeat measurements were performed.Results A total of 17 836 individuals were diagnosed with asthma during over 10 years of follow-up. Compared with the low-risk group, the HRs and 95% CIs for the highest PRS group and the poor sleep pattern group were 1.47 (95% CI: 1.41 to 1.52) and 1.55 (95% CI: 1.45 to 1.65), respectively. A combination of poor sleep and high genetic susceptibility led to a twofold higher risk compared with the low-risk combination (HR (95% CI): 2.22 (1.97 to 2.49), p

We adopt the two-point correlation function (2PCF) as a statistical tool to quantify the spatial clustering of halo stars for galaxy systems spanning a wide range in host halo virial mass ( $11.25\lt {\mathrm{log}}_{10}{M}_{200c}/{M}_{\odot }\lt 15$ ) and redshifts (0 < z < 1.5) from the IllustrisTNG simulations. Consistent with a previous study, we identify clear correlations between the strength of the 2PCF signals and galaxy formation redshifts, but over a much wider mass range. We find that such correlations are slightly stronger at higher redshifts and get weakened with the increase of host halo mass. We demonstrate that the spatial clustering of halo stars is affected by two factors: (1) the clustering gets gradually weakened as time passes (phase mixing); (2) newly accreted stars at more recent times would increase the clustering. For more massive galaxy systems, they assemble late, and the newly accreted stars would increase the clustering. The late assembly of massive systems may also help to explain the weaker correlations between the 2PCF signals and the galaxy formation redshifts in massive halos, as their 2PCFs are affected more by recently accreted stars, while formation redshift characterizes mass accretion on a much longer timescale. We find that the orbits of satellite galaxies in more massive halos maintain larger radial anisotropy, reflecting the more active accretion state of their hosts while also contributing to their stronger mass loss rates.

The two-point correlation function (2PCF) is a powerful statistical tool to measure galaxy clustering. Although 2PCF has also been used to study the clustering of stars on subparsec to kiloparsec scales, its physical implication is not clear. In this study, we use the Illustris-TNG50 simulation to study the connection between the 2PCF of accreted halo stars and the assembly histories of Milky Way-mass galaxies. We find, in general, that the 2PCF signal increases with the increase in galactocentric radii, r , and with the decrease in the pair separations. Galaxies that assemble late on average have stronger 2PCF signals. With z _1/4 , z _1/2 , and z _3/4 defined as the redshifts when galaxies accreted one-fourth, half, and three-fourths of their ex situ stellar mass today, we find they all show the strongest correlations with the 2PCF signals at r < ∼ 0.2 R _200 . z _3/4 shows the strongest correlations than those of z _1/4 or z _1/2 . However, the correlations have large scatters. The 2PCFs in the velocity space show weaker correlations with the galaxy formation times within ∼0.35 R _200 than real-space 2PCFs, and the scatter is considerably large. Both the real- and velocity-space 2PCFs correlate with the assembly histories of the host dark matter halos as well. Within 0.3 R _200 , the real-space 2PCF shows stronger correlations with the galaxy formation histories than with the halo formation histories. We conclude that it is difficult to use 2PCF alone to precisely predict the formation times or assembly histories of galaxies.

Heart-on-chip emerged as a potential tool for cardiac tissue engineering, recapitulating key physiological cues in cardiac pathophysiology. Controlled electrical stimulation and the ability to provide directly analyzed functional readouts are essential to evaluate the physiology of cardiac tissues in the heart-on-chip platforms. In this scenario, a novel heart-on-chip platform integrating two soft conductive hydrogel pillar electrodes was presented here. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts were seeded into the apparatus to create 3D human cardiac tissues. The application of electrical stimulation improved functional performance by altering the dynamics of tissue structure and contractile development. The contractile forces that cardiac tissues contract was accurately measured through optical tracking of hydrogel pillar displacement. Furthermore, the conductive properties of hydrogel pillars allowed direct and non-invasive electrophysiology studies, enabling continuous monitoring of signal changes in real-time while dynamically administering drugs to the cardiac tissues, as shown by a chronotropic reaction to isoprenaline and verapamil. Overall, the platform for acquiring contractile force and electrophysiological signals in situ allowed monitoring the tissue development trend without interrupting the culture process and could have diverse applications in preclinical drug testing, disease modeling, and therapeutic discovery.

IntroductionThe function of the autonomic nervous system (ANS) is crucial in the development of intradialytic hypotension (IDH). This study introduced the entropy of heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) to provide a complementary nonlinear and dynamic perspective for evaluating ANS function concerning IDH.Methods93 patients undergoing hemodialysis (HD) were enrolled, and the baseline data, electrocardiogram (ECG), and SKNA were collected. The patients were separated into the IDH and nonIDH groups based on the thresholds, which were characterized as reductions in systolic blood pressure (SBP) of at least 20 mm Hg or mean arterial pressure (MAP) of at least 10 mm Hg. We developed a logistic regression model for IDH after analyzing the changes in the time domain, frequency domain, the entropy of HRV, and SKNA indices during HD.ResultsAfter 4-h HD, the detected results for heart rate, the ratio of low frequency and high frequency (LF/HF), and average SKNA (aSKNA) all increased in both groups. Nine out of the ten HRV indices and aSKNA in the nonIDH group were higher than those in the IDH group at most moments. aSKNA was positively correlated with heart rate (p = 0.0001) and LF/HF (p = 0.0005) in the nonIDH group, while the correlation disappeared in the IDH group, which indicated a worse ANS response in IDH patients. The logistic regression model exhibited the results of initial SBP [odds ratio (OR) 1.076; p = 0.001], and the difference between the last and first segments (DLF) of heart rate [OR 1.101; p =0.012] and LF/HF [OR 0.209; p =0.034], as well as the extreme value of the difference between other segments and the first segments (EOF) of aSKNA [OR 2.908; p =0.017], which were independent indicators for IDH.DiscussionThe new nonlinear and dynamic assessment perspectives provided by the entropy of HRV and SKNA help to distinguish differences in ANS patterns between IDH patients and nonIDH patients and have the potential to be used in clinical monitoring for HD patients.

Obesity, a chronic metabolic disease with a complex pathophysiology, is caused by several variables. High-fat diets lead to the disruption of the gut microbiota and impaired gut barrier function in obese people. The dysbiosis and its metabolites through the intestinal barrier lead to an imbalance in energy metabolism and inflammatory response, which eventually contributes to the development of chronic diseases such as diabetes, hypertension, and cardiovascular disease. Current medicines are therapeutic to obesity in the short term; however, they may bring significant physical and emotional problems to patients as major side effects. Therefore, it is urgent to explore new therapeutic methods that have definite efficacy, can be taken for a long time, and have mild adverse effects. Numerous studies have demonstrated that traditional Chinese medicine (TCM) can control the gut microbiota in a multi-targeted and comprehensive manner, thereby restoring flora homeostasis, repairing damaged intestinal mucosal barriers, and eventually curbing the development of obesity. The active ingredients and compounds of TCM can restore the normal physiological function of the intestinal mucosal barrier by regulating gut microbiota to regulate energy metabolism, inhibit fat accumulation, affect food appetite, and reduce intestinal mucosal inflammatory response, thereby effectively promoting weight loss and providing new strategies for obesity prevention and treatment. Although there are some studies on the regulation of gut microbiota by TCM to prevent and treat obesity, all of them have the disadvantage of being systematic and comprehensive. Therefore, this work comprehensively describes the molecular mechanism of obesity mediated by gut microbiota based on the research state of obesity, gut microbiota, and TCM. A comprehensive and systematic summary of TCM targeting the regulation of gut microbiota for the treatment of obesity should be conducted in order to provide new strategies and ideas for the treatment of obesity.

The iPSC line was generated from the peripheral blood mononuclear cells (PBMCs) from a 53-year-old female patient carrying the LMNA gene mutation (c.1304_1307dup) diagnosed with atrial fibrillation and paroxysmal ventricular tachycardia. Through comprehensive detection, it was verified that the cell line had the LMNA gene mutation, normal karyotype, and the potential to differentiate into the three germ layers. This cell line may reveal potential therapeutic targets for atrial and ventricular arrhythmias caused by LMNA mutations.

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.

Background: Autonomic nerve system (ANS) plays an important role in regulating cardiovascular function and cerebrovascular function. Traditional heart rate variation (HRV) and emerging skin sympathetic nerve activity (SKNA) analyses from ultra-short-time (UST) data cannot fully reveal neural activity, thereby quantitatively reflect ANS intensity.Methods: Electrocardiogram and SKNA from sixteen patients (seven cerebral hemorrhage (CH) patients and nine control group (CO) patients) were recorded using a portable device. Ten derived HRV (mean, standard deviation and root mean square difference of sinus RR intervals (NNmean, SDNN and RMSSD), ultra-low frequency (

We generated an iPSCs line from the peripheral blood mononuclear cells (PBMCs) collected from a patient with long QT syndrome type 1 (LQT1) via a non-integrating system. We identified and verified a missense mutation in the KCNQ1 gene (c.773A > T) by whole-exome sequencing and Sanger sequencing. The established iPSC line was tested for pluripotency, differentiation potential, and karyotype. This cell-based model can help study the molecular mechanism and develop personalized drug therapies for LQT1.

The common approaches to control of skymions cause significant heat dissipation or require high electric fields near the breakdown threshold. Here, the authors demonstrate electric-field control of skyrmions through strain-mediated magnetoelectric coupling in multiferroic heterostructures.

Background: Autonomic nervous regulation plays a critical role in end-stage kidney disease (ESKD) patients with cardiovascular complications. However, studies on autonomic regulation in ESKD patients are limited to heart rate variability (HRV) analysis. Skin sympathetic nerve activity (SKNA), which noninvasively reflects the sympathetic nerve activity, has not been used in ESKD patients.Methods: Seventy-six patients on maintenance hemodialysis (MHD) treatment (a 4-h HD session, three times a week) were enrolled. Utilizing a noninvasive, single-lead, high-frequency recording system, we analyzed the dynamic change in HRV parameters and SKNA during HD. The different characteristics between the subgroups divided based on interdialytic weight gain (IDWG,

Peripheral blood mononuclear cells (PBMCs) were harvested and reprogramed to induced pluripotent stem cells (iPSCs) from a 46-year-old male patient with familial dilated cardiomyopathy and atrial fibrillation via a non-integrating system. A missense mutation in the LMNA gene (c.1003C > T) was identified by whole-exome sequencing and verified by Sanger sequencing. The pluripotency, differentiation potential, and karyotype of this cell line were also tested. This model is helpful to study the phenotype, mechanism, and therapy for laminopathy.

Evaluation of sympathetic nerve activity (SNA) using skin sympathetic nerve activity (SKNA) signal has attracted interest in recent studies. However, signal noises may obstruct the accurate location for the burst of SKNA, leading to the quantification error of the signal. In this study, we use the Teager–Kaiser energy (TKE) operator to preprocess the SKNA signal, and then candidates of burst areas were segmented by an envelope-based method. Since the burst of SKNA can also be discriminated by the high-frequency component in QRS complexes of electrocardiogram (ECG), a strategy was designed to reject their influence. Finally, a feature of the SKNA energy ratio (SKNAER) was proposed for quantifying the SKNA. The method was verified by both sympathetic nerve stimulation and hemodialysis experiments compared with traditional heart rate variability (HRV) and a recently developed integral skin sympathetic nerve activity (iSKNA) method. The results showed that SKNAER correlated well with HRV features (r = 0.60 with the standard deviation of NN intervals, 0.67 with low frequency/high frequency, 0.47 with very low frequency) and the average of iSKNA (r = 0.67). SKNAER improved the detection accuracy for the burst of SKNA, with 98.2% for detection rate and 91.9% for precision, inducing increases of 3.7% and 29.1% compared with iSKNA (detection rate: 94.5% (p < 0.01), precision: 62.8% (p < 0.001)). The results from the hemodialysis experiment showed that SKNAER had more significant differences than aSKNA in the long-term SNA evaluation (p < 0.001 vs. p = 0.07 in the fourth period, p < 0.01 vs. p = 0.11 in the sixth period). The newly developed feature may play an important role in continuously monitoring SNA and keeping potential for further clinical tests.

To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.

Long-term development of resource utilization has caused a series of economic, social, and ecological problems in resource-based cities (RBCs). Thus, in pursuit of sustainable urban development, many RBCs have begun seriously pursuing urban transformation and have achieved good results. However, the RBCs' urban resilience also exhibits evident stage characteristics throughout the processes of urban transformation. Herein, we constructed an evaluation index system to measure the urban resilience of Panzhihua, China and analyzed the resilience time-varying characteristics and influencing factors from 2000 to 2016. The results show that: (1) after undergoing urban transformation, changes in Panzhihua's resilience can be divided into three stages consisting of a slow rising period (2000-2005), a rapidly fluctuating rising period (2006-2010), and a stable development period (2011-2016). (2) Among the four divisions of urban resilience, the largest changes were found in the infrastructure and environment, and economic and social categories; only relatively small changes were observed in health and well-being, and government management capabilities. Nevertheless, all showed an upward trend. (3) Among the 12 indicators, transportation and communication, social security, education development, and comprehensive development ability were found to be closely linked to urban resilience. (4) Under the influence of urban transformation, RBCs' resilience greatly fluctuates, likely in response to actively transitioning the urban system from its previous state to its current state. Our study demonstrates that there is a high degree of correlation between the RBCs' life cycles and adaptation cycles.

This article discusses the necessity and possibilities of introducing ballet training into the process of teaching Chinese ethnic dance from theoretical and practical perspectives involving pedagogical analysis. We propose that there is a homologous and complementary relationship between ballet and Chinese ethnic dance in philosophy, aesthetic and technical goals, and desired outcomes. At the practical level, ballet, as a relatively mature, complete, and systematic dance training paradigm, plays and can further play a positive role in the traditional paradigm for teaching Chinese ethnic dance. The paper proposes several possible ways of the "absorption" and "embedding" of ballet training into the basic training of Chinese ethnic dance, which includes strengthening basic training in an appropriate manner. These combinations enhance dancers' physical coordination ability and technical skills, and they instill artistic values.