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Biodiversity, essential for sustainable development, faces threats from climate and land cover changes, which are the primary drivers of biodiversity loss. While previous studies have proposed approaches to identify priority protected areas (PPAs) for biodiversity conservation and simulated regional biodiversity responses to climate change or land cover change, however, they often fail to accurately identify PPAs and neglect the combined effects of climate and land cover changes on biodiversity. This study fills these gaps by proposing an integrated modeling approach with MaxEnt, InVEST, and Zonation to identify PPAs by prioritizing rare and endangered species, and exploring the spatial–temporal dynamics of these PPAs under the combined effects of climate and land cover changes from 2020 to 2050 by predicting land cover dynamics under the shared socioeconomic pathway (SSP) scenarios (SSP126, SSP245 and SSP585). Conservation gaps are revealed by spatial overlay analyses between these PPAs and existing protected areas. The spatial pattern of PPAs in Shenzhen is concentrated in the southeast with poor connectivity in the west. Primary PPAs are predominantly located in the southeast, secondary PPAs are mainly found on the periphery of the primary ones, and tertiary PPAs are scattered with limited connectivity across central, west, and northeast regions. From 2020 to 2050, biodiversity faces significant threats due to climate and land cover changes, resulting in a notable reduction in primary PPAs and increased habitat fragmentation within PPAs. In 2020, 70.19 % of the PPAs in Shenzhen were within existing PAs, with 89.66 % of primary PPAs covered. Conservation gaps are mainly in secondary and tertiary PPAs. Climate and land cover changes will diminish the effectiveness of existing PAs from 2020 to 2050. Spatial management suggestions for biodiversity conservation are proposed to mitigate challenges posed by climate and land cover changes.

This paper aims to address the challenge of precise robotic grasping of molecular sieve drying bags during automated packaging by proposing a six-dimensional (6D) pose estimation method based on an red green blue-depth (RGB-D) camera. The method consists of three components: point cloud pre-segmentation, target extraction, and pose estimation. A minimum bounding box-based pre-segmentation method was designed to minimize the impact of packaging wrinkles and skirt curling. Orientation filtering combined with Euclidean clustering and Principal Component Analysis (PCA)-based iterative segmentation was employed to accurately extract the target body. Lastly, a multi-target feature fusion method was applied for pose estimation to compute an accurate grasping pose. To validate the effectiveness of the proposed method, 102 sets of experiments were conducted and compared with classical methods such as Fast Point Feature Histograms (FPFH) and Point Pair Features (PPF). The results showed that the proposed method achieved a recognition rate of 99.02%, processing time of 2 s, pose error rate of 1.31%, and spatial position error of 3.278 mm, significantly outperforming the comparative methods. These findings demonstrated the effectiveness of the method in addressing the issue of accurate 6D pose estimation of molecular sieve drying bags, with potential for future applications to other complex-shaped objects.

Abstract New adjuvants that trigger cellular immune responses are urgently needed for the effective development of cancer and virus vaccines. Motivated by recent discoveries that show activation of type I interferon (IFN‐I) signaling boosts T cell immunity, this study proposes that targeting this pathway can be a strategic approach to identify novel vaccine adjuvants. Consequently, a comprehensive chemical screening of 6,800 small molecules is performed, which results in the discovery of the natural compound picrasidine S (PS) as an IFN‐I inducer. Further analysis reveals that PS acts as a powerful adjuvant, significantly enhancing both humoral and cellular immune responses. At the molecular level, PS initiates the activation of the cGAS‐IFN‐I pathway, leading to an enhanced T cell response. PS vaccination notably increases the population of CD8+ central memory (TCM)‐like cells and boosts the CD8+ T cell‐mediated anti‐tumor immune response. Thus, this study identifies PS as a promising candidate for developing vaccine adjuvants in cancer prevention.

Abstract Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3′ untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3′ untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.

Abstract Genome-wide association studies (GWASs) have identified thousands of non-coding variants that are associated with human complex traits and diseases. The analysis of such GWAS variants in different contexts and physiological states is essential for deciphering the regulatory mechanisms underlying human disease. Alternative polyadenylation (APA) is a key post-transcriptional modification for most human genes that substantially impacts upon cell behavior. Here, we mapped 9,493 3′-untranslated region APA quantitative trait loci in 18 human immune baseline cell types and 8 stimulation conditions (immune 3′aQTLs). Through the comparison between baseline and stimulation data, we observed the high responsiveness of 3′aQTLs to immune stimulation (response 3′aQTLs). Co-localization and mendelian randomization analyses of immune 3′aQTLs identified 678 genes where 3′aQTL are associated with variation in complex traits, 27.3% of which were derived from response 3′aQTLs. Overall, these analyses reveal the role of immune 3′aQTLs in the determination of complex traits, providing new insights into the regulatory mechanisms underlying disease etiologies.

Introduction: Mesenchymal stem cells (MSCs) possess a high degree of self-renewal capacity and in vitro multi-lineage differentiation potential. Decellularized materials have garnered considerable attention due to their elevated biocompatibility, reduced immunogenicity, excellent biodegradability, and the ability to partially mimic the in vivo microenvironment conducive to cell growth. To address the issue of mesenchymal stem cells losing their stem cell characteristics during two-dimensional (2D) cultivation, this study established three-dimensional cell carriers modified with lung decellularized extracellular matrix and assessed its impact on the life activities of mesenchymal stem cells.Methods: This study employed PET as a substrate material, grafting with polydopamine (PDA), and constructing a decellularized extracellular matrix (dECM) coating on its surface, thus creating the PET/PDA/dECM three-dimensional (3D) composite carrier. Subsequently, material characterization of the cellular carriers was conducted, followed by co-culturing with human umbilical cord mesenchymal stem cells in vitro, aiming to investigate the material’s impact on the proliferation and paracrine activity of mesenchymal stem cells.Results and Discussion: Material characterization demonstrated successful grafting of PDA and dECM materials, and it had complete hydrophilicity, high porosity, and excellent mechanical properties. The material was rich in various ECM proteins (collagen I, collagen IV , laminin, fibronectin, elastin), indicating good biocompatibility. In long-term in vitro cultivation (14 days) experiments, the PET/PDA/dECM three-dimensional composite carrier significantly enhanced adhesion and proliferation of human umbilical cord-derived mesenchymal stem cells (HUCMSCs), with a proliferation rate 1.9 times higher than that of cells cultured on tissue culture polystyrene (TCPS) at day 14. Furthermore, it effectively maintained the stem cell characteristics, expressing specific antigens for HUCMSCs. Through qPCR, Western blot, and ELISA experiments, the composite carrier markedly promoted the expression and secretion of key cell factors in HUCMSCs. These results demonstrate that the PET/PDA/dECM composite carrier holds great potential for scaling up MSCs’ long-term in vitro cultivation and the production of paracrine factors.

Traditional single nucleic acid assays can only detect one target while multiple nucleic acid assays can detect multiple targets simultaneously, providing comprehensive and accurate information. Fluorescent microspheres in multiplexed nucleic acid detection offer high sensitivity, specificity, multiplexing, flexibility, and scalability advantages, enabling precise, real-time results and supporting clinical diagnosis and research. However, multiplexed assays face challenges like complexity, costs, and sample handling issues. The review explores the recent advancements and applications of fluorescent microspheres in multiple nucleic acid detection. It discusses the versatility of fluorescent microspheres in various fields, such as disease diagnosis, drug screening, and personalized medicine. The review highlights the possibility of adjusting the performance of fluorescent microspheres by modifying concentrations and carrier forms, allowing for tailored applications. It emphasizes the potential of fluorescent microsphere technology in revolutionizing nucleic acid detection and advancing health, disease treatment, and medical research.

Epigenetic status–altering mutations in chromatin-modifying enzymes are a feature of human diseases, including many cancers. However, the functional outcomes and cellular dependencies arising from these mutations remain unresolved. In this study, we investigated cellular dependencies, or vulnerabilities, that arise when enhancer function is compromised by loss of the frequently mutated COMPASS family members MLL3 and MLL4. CRISPR dropout screens in MLL3/4-depleted mouse embryonic stem cells (mESCs) revealed synthetic lethality upon suppression of purine and pyrimidine nucleotide synthesis pathways. Consistently, we observed a shift in metabolic activity toward increased purine synthesis in MLL3/4-KO mESCs. These cells also exhibited enhanced sensitivity to the purine synthesis inhibitor lometrexol, which induced a unique gene expression signature. RNA-Seq identified the top MLL3/4 target genes coinciding with suppression of purine metabolism, and tandem mass tag proteomic profiling further confirmed upregulation of purine synthesis in MLL3/4-KO cells. Mechanistically, we demonstrated that compensation by MLL1/COMPASS was underlying these effects. Finally, we demonstrated that tumors with MLL3 and/or MLL4 mutations were highly sensitive to lometrexol in vitro and in vivo, both in culture and in animal models of cancer. Our results depicted a targetable metabolic dependency arising from epigenetic factor deficiency, providing molecular insight to inform therapy for cancers with epigenetic alterations secondary to MLL3/4 COMPASS dysfunction.

Chimeric antigen receptor (CAR) T-cell based immunotherapy has shown its potential in treating blood cancers, and its application to solid tumors is currently being extensively investigated. For glioma brain tumors, various CAR T-cell targets include IL13Rα2, EGFRvIII, HER2, EphA2, GD2, B7-H3, and chlorotoxin. In this work, we are interested in developing a mathematical model of IL13Rα2 targeting CAR T-cells for treating glioma. We focus on extending the work of Kuznetsov et al. (1994) by considering binding of multiple CAR T-cells to a single glioma cell, and the dynamics of these multi-cellular conjugates. Our model more accurately describes experimentally observed CAR T-cell killing assay data than the models which do not consider multi-cellular conjugates. Moreover, we derive conditions in the CAR T-cell expansion rate that determines treatment success or failure. Finally, we show that our model captures distinct CAR T-cell killing dynamics from low to high antigen receptor densities in patient-derived brain tumor cells.

Abstract Background With a high prevalence of noise-induced hearing loss (NIHL), the noise survey tools for identifying individuals with high risk of NIHL are still limited. This study was aimed to translate and develop a Chinese version of noise exposure questionnaire (C-NEQ), and validate its reliability and reproducibility. Methods This study was conducted from May 2020 to March 2021 in China. The questionnaire was translated from the original NEQ and adapted into Chinese culture using the method according to the International Test Committee. Content validity was evaluated by our expert group. Construct validity and reliability of the C-NEQ was determined through estimating the confirmatory factor analysis and Cronbach’s alpha in a cross-sectional analysis among 641 Chinese speaking adults, respectively. The retest reproducibility of the C-NEQ was analyzed by using the intra-group correlation coefficient (ICC) in a follow-up analysis among 151 participants. Results The C-NEQ comprises ten items covering four domains: occupational, housework, transport and recreational noise exposure. The annual noise exposure (ANE) was calculated as the protocol of original NEQ. A total of 641 adult participants (aged 26.9 ± 10.1 years, 53.4% males) completed the C-NEQ. The average time for completing the C-NEQ was 4.4 ± 3.0 min. Content validity indicated high relevance of the C-NEQ. The confirmatory factor analysis indices illustrated that the items of the C-NEQ were suitable with the data in the study. For the internal reliability, the Cronbach’s α coefficients of the total items and four domains (occupational, housework, transport, and recreational noise exposure) were 0.799, 0.959, 0.837, 0.825, and 0.803, respectively. Among them, 151 participants (aged 36.1 ± 11.1 years, 65.6% males) completed the retest of the C-NEQ 1 month after the first test. The ICC value of total ANEs between the first test and the second test was 0.911 (P

In order to achieve the objectivity and accuracy of the evaluation of fabric pilling performance, a new objective evaluation of fabric pilling grade based on visual saliency model is proposed. First of all, the local feature saliency mechanism-Gaussian pyramid decomposition was used to achieve that pilling was separated from the uneven information of fabric texture and illumination. And the center-surround operation was used to obtain the saliency images of fabric pilling defects. Then the global feature saliency mechanism-spectral residual method was used to improve the saliency of fabric pilling defects, and mean structural similarity was used to evaluate the quality of fabric pilling saliency images. Finally, the fabric pilling interest images was obtained by Gaussian fitting threshold segmentation, and the pilling feature parameters were extracted for grade evaluation. The results show that the algorithm can enhance the pilling saliency and obtain effective pilling characteristic parameters, and realize the accurate evaluation of 1～5 fabric pilling grade.

Abstract Background Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system. Limited knowledge of prestin is from experiments using site-directed mutagenesis or domain-swapping techniques after the amino acid residues were identified by comparing the sequence of prestin to those of its paralogs and orthologs. Frog prestin is the only representative in amphibian lineage and the studies of it were quite rare with only one species identified. Results Here we report a new coding sequence of SLC26A5 for a frog species, Rana catesbeiana (the American bullfrog). In our study, the SLC26A5 gene of Rana has been mapped, sequenced and cloned successively using RNA-Seq. We measured the nonlinear capacitance (NLC) of prestin both in the hair cells of Rana’s inner ear and HEK293T cells transfected with this new coding gene. HEK293T cells expressing Rana prestin showed electrophysiological features similar to that of hair cells from its inner ear. Comparative studies of zebrafish, chick, Rana and an ancient frog species showed that chick and zebrafish prestin lacked NLC. Ancient frog’s prestin was functionally different from Rana. Conclusions We mapped and sequenced the SLC26A5 of the Rana catesbeiana from its inner ear cDNA using RNA-Seq. The Rana SLC26A5 cDNA was 2292 bp long, encoding a polypeptide of 763 amino acid residues, with 40% identity to mammals. This new coding gene could encode a functionally active protein conferring NLC to both frog HCs and the mammalian cell line. While comparing to its orthologs, the amphibian prestin has been evolutionarily changing its function and becomes more advanced than avian and teleost prestin.

For mechanical equipment, the wear particle in the lubrication system during equipment operation can reflect the lubrication condition, wear mechanism, and severity of wear between equipment friction pairs. To solve the problems of false detection and missed detection of small, dense, and overlapping wear particles in the current ferrography wear particle detection model in a complex oil background environment, a new ferrography wear particle detection network, EYBNet, is proposed. Firstly, the MSRCR algorithm is used to enhance the contrast of wear particle images and reduce the interference of complex lubricant backgrounds. Secondly, under the framework of YOLOv5s, the accuracy of network detection is improved by introducing DWConv and the accuracy of the entire network is improved by optimizing the loss function of the detection network. Then, by adding an ECAM to the backbone network of YOLOv5s, the saliency of wear particles in the images is enhanced, and the feature expression ability of wear particles in the detection network is enhanced. Finally, the path aggregation network structure in YOLOv5s is replaced with a weighted BiFPN structure to achieve efficient bidirectional cross-scale connections and weighted feature fusion. The experimental results show that the average accuracy is increased by 4.46%, up to 91.3%, compared with YOLOv5s, and the detection speed is 50.5FPS.

Abstract Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. Transcriptionally, FOXA1, GATA3, and PPARG are shown to be essential for luminal subtype-specific gene regulation and subtype switching, while TP63, STAT3, and TFAP2 family members are critical for regulation of basal subtype-specific genes. Despite these advances, the underlying epigenetic mechanisms and 3D chromatin architecture responsible for subtype-specific regulation in bladder cancer remain unknown. Result We determine the genome-wide transcriptome, enhancer landscape, and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration. Conclusion In summary, our work identifies unique epigenomic signatures and 3D genome structures in luminal and basal urinary bladder cancers and suggests a novel link between the circadian transcription factor NPAS2 and a clinical bladder cancer subtype.

Abstract Background Significant sex differences exist in hearing physiology, while few human studies have investigated sex differences in noise-induced hearing loss (NIHL), and the sex bias in previous studies resulted in inadequate female data. The study aims to investigate sex differences in the characteristics of NIHL to provide insight into sex-specific risk factors, prevention strategies and treatment for NIHL. Methods This cross-sectional study included 2280 industrial noise-exposed shipyard workers (1140 males and 1140 females matched for age, job and employment length) in China. Individual noise exposure levels were measured to calculate the cumulative noise exposure (CNE), and an audiometric test was performed by an experienced technician in a soundproof booth. Sex differences in and influencing factors of low-frequency (LFHL) and high-frequency hearing loss (HFHL) were analyzed using logistic regression models stratified by age and CNE. Results At comparable noise exposure levels and ages, the prevalence of HFHL was significantly higher in males (34.4%) than in females (13.8%), and males had a higher prevalence of HFHL (OR = 4.19, 95% CI 3.18 to 5.52) after adjusting for age, CNE, and other covariates. Sex differences were constant and highly remarkable among subjects aged 30 to 40 years and those with a CNE of 80 to 95 dB(A). Alcohol consumption might be a risk factor for HFHL in females (OR = 3.12, 95% CI 1.10 to 8.89). Conclusions This study indicates significant sex differences in NIHL. Males are at higher risk of HFHL than females despite equivalent noise exposure and age. The risk factors for NIHL might be different in males and females.

Background: The basement membrane (BM) serves as a major barrier to impede tumor cell invasion and extravasation during metastasis. However, the associations between BM-related genes and GC remain unclear. Methods: RNA expression data and corresponding clinical information of STAD samples were downloaded from the TCGA database. We identified BM-related subtypes and constructed a BM-related gene prognostic model using lasso-Cox regression analysis. We also investigated the single-cell properties of prognostic-related genes and the TME characteristic, TMB status, and chemotherapy response in high- and low-risk groups. Finally, we verified our results in the GEPIA database and human tissue specimens. Results: A six-gene lasso Cox regression model (APOD, CAPN6, GPC3, PDK4, SLC7A2, SVEP1) was developed. Activated CD4+ T cells and follicular T cells were shown to infiltrate more widely in the low-risk group. The low-risk group harbored significantly higher TMB and better prognosis, favoring immunotherapy. Conclusions: We constructed a six-gene BM-related prognostic model for predicting GC prognosis, immune cell infiltration, TMB status, and chemotherapy response. This research provides new ideas for developing more effective individualized treatment of GC patients.

China’s high-tech industrial development zones (HIDZs) is a key “place-based” policy targeting national innovation-driven development. Despite the extensive research on HIDZs, it remains unclear whether and to what extent the policy has fostered cities’ innovation output and quality. Basing our research on panel data of Chinese cities from 2001 to 2019, we employed the PSM-DID model to examine the impact of HIDZs policy on their host cities’ innovation output and quality. The empirical results show that: (1) In general, the establishment of HIDZs has a more significant positive effect on fostering urban innovation output compared to its role in promoting urban innovation quality. However, (2) the effect on urban innovation output and quality varies across different cities. For cities with more advantageous locations and policies, HIDZ policy plays a more instrumental role in promoting the quality of urban innovation, while the establishment of HIDZs in other cities is more conducive to increasing the output of urban innovation. Ultimately, we argue that authorities must recognize the importance of integrated development of HIDZs and their host cities and incorporating HIDZs’ impact on the host cities into the HIDZ evaluation. It is necessary to understand that HIDZs have multiple development modes due to their specific local conditions. Hence, differentiated guidance must be carried out rather than directly replicating the experience from developed regions.

Four Chinese herbs from the Citrus genus, namely Aurantii Fructus Immaturus (Zhishi), Aurantii Fructus (Zhiqiao), Citri Reticulatae Pericarpium Viride (Qingpi) and Citri Reticulatae Pericarpium (Chenpi), are widely used for treating various cardiovascular and gastrointestinal diseases. Many ingredients have already been identified from these herbs, and their various bioactivities provide some interpretations for the pharmacological functions of these herbs. However, the complex functions of these herbs imply undisclosed cholinergic activity. To discover some ingredients with cholinergic activity and further clarify possible reasons for the complex pharmacological functions presented by these herbs, depending on the extended structure–activity relationships of cholinergic and anti-cholinergic agents, a simple method was established here for quickly discovering possible choline analogs using a specific TLC method, and then stachydrine and choline were first identified from these Citrus herb decoctions based on their NMR and HRMS data. After this, two TLC scanning (TLCS) methods were first established for the quantitative analyses of stachydrine and choline, and the contents of the two ingredients and synephrine in 39 samples were determined using the valid TLCS and HPLC methods, respectively. The results showed that the contents of stachydrine (3.04‰) were 2.4 times greater than those of synephrine (1.25‰) in Zhiqiao and about one-third to two-thirds of those of Zhishi, Qingpi and Chenpi. Simultaneously, the contents of stachydrine, choline and synephrine in these herbs present similar decreasing trends with the delay of harvest time; e.g., those of stachydrine decrease from 5.16‰ (Zhishi) to 3.04‰ (Zhike) and from 1.98‰ (Qingpi) to 1.68‰ (Chenpi). Differently, the contents of synephrine decrease the fastest, while those of stachydrine decrease the slowest. Based on these results, compared with the pharmacological activities and pharmacokinetics reported for stachydrine and synephrine, it is indicated that stachydrine can be considered as a bioactive equilibrist for synephrine, especially in the cardio-cerebrovascular protection from these citrus herbs. Additionally, the results confirmed that stachydrine plays an important role in the pharmacological functions of these citrus herbs, especially in dual-directionally regulating the uterus, and in various beneficial effects on the cardio-cerebrovascular system, kidneys and liver.

ObjectiveIschemic stroke (IS) with subsequent cerebrocardiac syndrome (CCS) has a poor prognosis. We aimed to investigate electrocardiogram (ECG) changes after IS with artificial intelligence (AI).MethodsWe collected ECGs from a healthy population and patients with IS, and then analyzed participant demographics and ECG parameters to identify abnormal features in post-IS ECGs. Next, we trained the convolutional neural network (CNN), random forest (RF) and support vector machine (SVM) models to automatically detect the changes in the ECGs; Additionally, We compared the CNN scores of good prognosis (mRS ≤ 2) and poor prognosis (mRS > 2) to assess the prognostic value of CNN model. Finally, we used gradient class activation map (Grad-CAM) to localize the key abnormalities.ResultsAmong the 3506 ECGs of the IS patients, 2764 ECGs (78.84%) led to an abnormal diagnosis. Then we divided ECGs in the primary cohort into three groups, normal ECGs (N-Ns), abnormal ECGs after the first ischemic stroke (A-ISs), and normal ECGs after the first ischemic stroke (N-ISs). Basic demographic and ECG parameter analyses showed that heart rate, QT interval, and P-R interval were significantly different between 673 N-ISs and 3546 N-Ns (p < 0.05). The CNN has the best performance among the three models in distinguishing A-ISs and N-Ns (AUC: 0.88, 95%CI = 0.86-0.90). The prediction scores of the A-ISs and N-ISs obtained from the all three models are statistically different from the N-Ns (p < 0.001). Futhermore, the CNN scores of the two groups (mRS > 2 and mRS ≤ 2) were significantly different (p < 0.05). Finally, Grad-CAM revealed that the V4 lead may harbor the highest probability of abnormality.ConclusionOur study showed that a high proportion of post-IS ECGs harbored abnormal changes. Our CNN model can systematically assess anomalies in and prognosticate post-IS ECGs.

Due to the characteristics of inductance parameter mismatch and back electromotive force harmonics caused by novel leakage flux branches and other non-ideal factors for the variable-leakage-flux permanent magnet (VLF-PM) motor, its control system suffers from a deteriorated performance of the rotor position estimation. To overcome the problems mentioned above, an adaptive tracking estimator of the rotor position is proposed in this paper for the VLF-PM motor control system. First, the proposed method simplifies the VLF-PM motor mathematical model and reduces the effect of inductance parameter variations according to the active flux concept. Then, robust and gradient descent algorithms are utilized to maintain the robustness of inductance parameter variations and eliminate the specific order harmonics owing to the novel leakage flux branches. Meanwhile, the accuracy and stability are enhanced. Furthermore, the position compensation based on the current adaptive tracking strategy is proposed to compensate the rotor position error caused by other non-ideal factors. Finally, the feasibility of the proposed estimated system is verified.

Titanium body porcelains were synthesised through the sol-gel combustion method by using carbamide and glycine as the composite organic fuels with a mole ratio of 7:3. Then the synthesised porcelain was microwave fused on the Ti surface. The porcelain was characterised by X-ray diffraction and scanning electron microscope tests. The XRD results showed that the body porcelains ignited at 400, 500 and 600 °C were all amorphous. When the ignited temperature is only 400 °C, some crystalline diffraction peaks of KNO3 existed due to the incomplete combustion reaction. When the igniting temperature was elevated to 500 and 600 °C or a higher ratio of fuel to nitrates (1.25:1 and 1.5:1) was employed, the nitrates completely reacted and there was no obvious nitrate residue. The size and quantity of the pores slightly increased with the ratio of fuel to nitrates increased from 1:1 to 1.5:1. A dense coating with a homogeneous vitreous structure was fused on the Ti surface by microwaves.

Objective: To compare the hearing screening results of two-step transient evoked otoacoustic emissions (TEOAE) and one-step automatic auditory brainstem response (AABR) in non-risk newborns, and to explore a more suitable hearing screening protocol for infants discharged within 48 h after birth in remote areas of China.Methods: To analyze the age effect on pass rate for hearing screening, 2005 newborns were divided into three groups according to screening time after birth:

ObjectivesThe objective of the study was to identify the acute high-intensity recreational noise-induced effects on auditory function, especially the cochlear synaptopathy-related audiological metrics, in humans with normal hearing.MethodsThis prospective cohort study enrolled 32 young adults (14 males and 18 females); the mean age was 24.1 ± 2.4 years (ranging from 20 to 29). All participants with normal hearing (audiometric thresholds ≤25 dB HL at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for both ears) had already decided to participate in the outdoor music festival. Participants were asked to measure the noise exposure dose and complete auditory examinations, including the air-conduction pure-tone audiometry (PTA), distortion product otoacoustic emission (DPOAE), contralateral suppression (CS) on transient evoked otoacoustic emission (TEOAE), auditory brainstem response (ABR) test and Mandarin Hearing in Noise Test (MHINT), at baseline and 1 day and 14 days after music festival noise exposure.ResultsThe mean time of attending the music festival was 7.34 ± 0.63 h (ranging from 6.4 to 9.5), the mean time-weighted average (TWA) of noise exposure dose was 93.2 ± 2.39 dB(A) (ranging from 87.9 to 97.7). At neither 1 day nor 14 days post exposure, there were no statistically significant effects on PTA thresholds, DPOAE amplitudes, CS on TEOAEs, or MHINT signal-to-noise ratios (SNRs) of acute outdoor music festival noise exposure, regardless of sex. While the ABR wave I amplitudes significantly decreased at 1 day after exposure and recovered at 14 days after exposure, the exposed/unexposed ABR wave I amplitude ratio was significantly correlated with MHINT SNR change at 1 day after exposure, although it was not correlated with the noise exposure dose.ConclusionIn young adults with normal hearing, we found the self-compared decrement of ABR wave I amplitudes at 1 day post acute recreational noise exposure at high intensity, which also contributes to the change in speech perceptual ability in noisy backgrounds. This study indicated that auditory electrophysiological metric changes might be a more sensitive and efficient indicator of noise-induced cochlear synaptic dysfunction in humans. More attention should be paid to the recreational noise-induced cochlear synaptopathy and auditory perceptual disorder.

During early mammalian embryo development, a small number of cells make robust fate decisions at particular spatial locations in a tight time window to form inner cell mass (ICM), and later epiblast (Epi) and primitive endoderm (PE). While recent single-cell transcriptomics data allows scrutinization of heterogeneity of individual cells, consistent spatial and temporal mechanisms the early embryo utilize to robustly form the Epi/PE layers from ICM remain elusive. Here we build a multiscale three-dimensional model for mammalian embryo to recapitulate the observed patterning process from zygote to late blastocyst. By integrating the spatiotemporal information reconstructed from multiple single-cell transcriptomic datasets, the data-informed modeling analysis suggests two major processes critical to the formation of Epi/PE layers: a selective cell-cell adhesion mechanism (via EphA4/EphrinB2) for fate-location coordination and a temporal attenuation mechanism of cell signaling (via Fgf). Spatial imaging data and distinct subsets of single-cell gene expression data are then used to validate the predictions. Together, our study provides a multiscale framework that incorporates single-cell gene expression datasets to analyze gene regulations, cell-cell communications, and physical interactions among cells in complex geometries at single-cell resolution, with direct application to late-stage development of embryogenesis.

Background: The definition of notched audiogram for noise-induced hearing loss (NIHL) is presently based on clinical experience, but audiometric phenotypes of NIHL are highly heterogeneous. The data-driven clustering of subtypes could provide refined characteristics of NIHL, and help identify individuals with typical NIHL at diagnosis.Methods: This cross-sectional study initially recruited 12,218 occupational noise-exposed employees aged 18–60 years from two factories of a shipyard in Eastern China. Of these, 10,307 subjects with no history of otological injurie or disease, family history of hearing loss, or history of ototoxic drug use were eventually enrolled. All these subjects completed health behavior questionnaires, cumulative noise exposure (CNE) measurement, and pure-tone audiometry. We did data-driven cluster analysis (k-means clustering) in subjects with hearing loss audiograms (n = 6,599) consist of two independent datasets (n = 4,461 and n = 2,138). Multinomial logistic regression was performed to analyze the relevant characteristics of subjects with different audiometric phenotypes compared to those subjects with normal hearing audiograms (n = 3,708).Results: A total of 10,307 subjects (9,165 males [88.9%], mean age 34.5 [8.8] years, mean CNE 91.2 [22.7] dB[A]) were included, 3,708 (36.0%) of them had completely normal hearing, the other 6,599 (64.0%) with hearing loss audiograms were clustered into four audiometric phenotypes, which were replicable in two distinct datasets. We named the four clusters as the 4–6 kHz sharp-notched, 4–6 kHz flat-notched, 3–8 kHz notched, and 1–8 kHz notched audiogram. Among them, except for the 4–6 kHz flat-notched audiogram which was not significantly related to NIHL, the other three phenotypes with different relevant characteristics were strongly associated with noise exposure. In particular, the 4–6 kHz sharp-notched audiogram might be a typical subtype of NIHL.Conclusions: By data-driven cluster analysis of the large-scale noise-exposed population, we identified three audiometric phenotypes associated with distinct NIHL subtypes. Data-driven sub-stratification of audiograms might eventually contribute to the precise diagnosis and treatment of NIHL.

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

The prestin-based active process in the mammalian outer hair cells (OHCs) is believed to play a crucial role in auditory signal amplification in the cochlea. Prestin belongs to an anion transporter family (SLC26A). It is densely expressed in the OHC lateral plasma membrane and functions as a voltage-dependent motor protein. Analog genes can be found in the genome of nonmammalian species, but their functions in hearing are poorly understood. In the present study, we used the gerbil prestin sequence as a template and identified an analog gene in the bullfrog genome. We expressed the gene in a stable cell line (HEK293T) and performed patch-clamp recording. We found that these cells exhibited prominent nonlinear capacitance (NLC), a widely accepted assay for prestin functioning as a motor protein. Upon close examination, the key parameters of this NLC are comparable to that conferred by the gerbil prestin, and nontransfected cells failed to display NLC. Lastly, we performed patch-clamp recording in HCs of all three hearing organs in bullfrog. HCs in both the sacculus and the amphibian papilla exhibited a capacitance profile that is similar to NLC while HCs in the basilar papilla showed no sign of NLC. Whether or not this NLC-like capacitance change is involved in auditory signal amplification certainly requires further examination; our results represent the first and necessary step in revealing possible roles of prestin in the active hearing processes found in many nonmammalian species.

Swimming by shape changes at low Reynolds number is widely used in biology andunderstanding how the performance of movement depends on the geometric pattern ofshape changes is important to understand swimming of microorganisms and in designing lowReynolds number swimming models. Thesimplest models of shape changes are those that comprise a series of linkedspheres that can change their separation and/or their size. Herein we comparethe performance of three models in which these modes are used in different ways.

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.

Optimal gait design is important for micro-organisms and micro-robots that propel themselves in a fluid environment in the absence of external force or torque. The simplest models of shape changes are those that comprise a series of linked-spheres that can change their separation and/or their sizes. We examine the dynamics of three existing linked-sphere types of modeling swimmers in low Reynolds number Newtonian fluids using asymptotic analysis, and obtain their optimal swimming strokes by solving the Euler−Lagrange equation using the shooting method. The numerical results reveal that (1) with the minimal 2 degrees of freedom in shape deformations, the model swimmer adopting the mixed shape deformation modes strategy is more efficient than those with a single-mode of shape deformation modes, and (2) the swimming efficiency mostly decreases as the number of spheres increases, indicating that more degrees of freedom in shape deformations might not be a good strategy in optimal gait design in low Reynolds number locomotion.

A critical event in mammalian embryo development is construction of an inner cell mass surrounded by a trophoectoderm (a shell of cells that later form extraembryonic structures). We utilize multi-scale, stochastic modeling to investigate the design principles responsible for robust establishment of these structures. This investigation makes three predictions, each supported by our quantitative imaging. First, stochasticity in the expression of critical genes promotes cell plasticity and has a critical role in accurately organizing the developing mouse blastocyst. Second, asymmetry in the levels of noise variation (expression fluctuation) of Cdx2 and Oct4 provides a means to gain the benefits of noise-mediated plasticity while ameliorating the potentially detrimental effects of stochasticity. Finally, by controlling the timing and pace of cell fate specification, the embryo temporally modulates plasticity and creates a time window during which each cell can continually read its environment and adjusts its fate. These results suggest noise has a crucial role in maintaining cellular plasticity and organizing the blastocyst.

A fundamental question in biology is how sharp boundaries of gene expression form precisely in spite of biological variation/noise. Numerous mechanisms position gene expression domains across fields of cells (e.g. morphogens), but how these domains are refined remains unclear. In some cases, domain boundaries sharpen through differential adhesion-mediated cell sorting. However, boundaries can also sharpen through cellular plasticity, with cell fate changes driven by up- or down-regulation of gene expression. In this context, we have argued that noise in gene expression can help cells transition to the correct fate. Here we investigate the efficacy of cell sorting, gene expression plasticity, and their combination in boundary sharpening using multi-scale, stochastic models. We focus on the formation of hindbrain segments (rhombomeres) in the developing zebrafish as an example, but the mechanisms investigated apply broadly to many tissues. Our results indicate that neither sorting nor plasticity is sufficient on its own to sharpen transition regions between different rhombomeres. Rather the two have complementary strengths and weaknesses, which synergize when combined to sharpen gene expression boundaries.