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Mengdi Zhang,1 Dongqing Pu,1 Dandan Feng,1 Guangxi Shi,2 Jingwei Li2 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan City, People’s Republic of China; 2Department of Thyroid and Breast Diagnosis and Treatment Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, People’s Republic of ChinaCorrespondence: Jingwei Li, Department of Thyroid and Breast Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, People’s Republic of China, Email 71000395@sdutcm.edu.cnPurpose: Granulomatous mastitis (GLM) is a rare and complex chronic inflammatory disease of the breast with an unknown cause and a tendency to recur. As medical science advances, the cause, treatment strategies, and comprehensive management of GLM have increasingly attracted widespread attention. The aim of this study is to assess the development trends and research focal points in the GLM field over the past 24 years using bibliometric analysis.Methods: Using GLM, Granulomatous mastitis (GM), Idiopathic granulomatous lobular mastitis (IGLM), and Idiopathic granulomatous mastitis (IGM) as keywords, we retrieved publications related to GLM from 2000 to 2023 from the Web of Science, excluding articles irrelevant to this study. Citespace and VOSviewer were employed for data analysis and visualization.Results: A total of 347 publications were included in this analysis. Over the past 24 years, the number of publications has steadily increased, with Turkey being the leading contributor in terms of publications and citations. The University of Health Sciences, Istanbul University, and Istanbul University Cerrahpasa were the most influential institutions. The Breast Journal, Breast Care, and Journal of Investigative Surgery were the journals that published the most on this topic. The research primarily focused on the cause, differential diagnosis, treatment, and comprehensive management of GLM. Issues related to recurrence, hyperprolactinemia, and Corynebacterium emerged as current research hotspots.Conclusion: Our bibliometric study outlines the historical development of the GLM field and identifies recent research focuses and trends, which may aid researchers in identifying research hotspots and directions, thereby advancing the study of GLM.Keywords: granulomatous lobular mastitis, bibliometric analysis, visual analysis, knowledge graphs, review

Dan Pu, Shiyong Zhang, Shoushan Hu, Yuyao Zhang, Xin Xiong, Shufang Du State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Shufang Du; Xin Xiong, Email dushufang@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aims to investigate the relationship between oral health-related quality of life (OHRQoL) and emotional distress (ED), including anxiety and depression, in orthodontic patients.Methods: A cross-sectional study was conducted involving 603 orthodontic patients, consisting of 401 females (66.5%) with a mean age of 24.15 ± 7.72 and 202 males (33.5%) with a mean age of 24.16 ± 7.72. A questionnaire containing questions of demographic information, the Oral Health Impact Profile (OHIP-14) and the Huaxi emotional-distress index (HEI) was employed to assess OHRQoL and ED. According to the HEI score, the respondents were divided into ED group (HEI > 8) and non-ED group (HEI ≤ 8). Data were analyzed using Kolmogorov–Smirnov test, Mann–Whitney test and logistic regression analysis with the significance level set at p < 0.05.Results: The prevalence of poor OHRQoL and ED of the study sample was 28.4% and 19.57%, respectively. There was a significantly higher prevalence of ED among poor OHRQoL patients (35.67%) compared to those with good OHRQoL (13.19%) (p < 0.001). Poor OHRQoL and risky drinking behavior addressed higher significant correlation with ED patients than non-ED patients (p < 0.05). There were no statistical differences in other factors such as gender, age, and appliance type (p > 0.05). Poor OHRQoL orthodontic patients were at a higher risk of suffering from anxiety and depression compared to those with good OHRQoL (age-risky drinking behavior-sex-adjusted: OR = 4.00; all p < 0.001).Conclusion: Oral health-related quality of life (OHRQoL) is related to emotional stress. Namely, patients with poor OHRQoL are more likely to experience anxiety and depression. As a result, orthodontists should consistently assess the emotional well-being and OHROoL of patients over the treatment course for better treatment outcomes.Keywords: orthodontic patients, oral health-related quality of life, emotional distress, anxiety, depression, cross-sectional study

Weiling Leng,1 Danlan Pu,2 Juan Jiang,2 Xiaotian Lei,1 Qinan Wu,3,&ast; Bing Chen1,&ast; 1Endocrinology Department, The First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, People’s Republic of China; 3Endocrinology Department, Chongqing Medical University Affiliated Dazu Hospital, Dazu District People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinan Wu; Bing Chen Email wqn11@126.com; chenbingxnyy@126.comBackground: This study investigated the effects of metformin on breast density in overweight/obese premenopausal women.Methods: Overweight/obese premenopausal women (n=120) were randomly assigned to the metformin or placebo group, and all women received lifestyle interventions. The outcomes included weight, BMI, FPG, FIN, glucose, HOMA-IR, LDL-C, HDL-C, TG, TC, SBP, DBP, FSH, E, AD, and the BIRADS grade, and the incidence of breast cancer was assessed by pathological biopsy and BIRADS grade greater than 4.Results: In total, 120 overweight/obese women completed the 1-year trial. Seven patients had a BIRADS grade greater than 4, including 5 patients who were biopsy positive, in the control group, and 2 patients had a BIRADS grade greater than 4, including 1 patient who was biopsy positive, in the metformin group. Compared with those in the control group, the body weight, BMI, FIN, FPG, HOMA-IR, TC, BIRADS grade and positive pathological biopsy rate in the metformin group were significantly decreased (P< 0.05), while AD was significantly increased (P< 0.05). The correlation analysis indicated that the BIRADS grade was significantly correlated with weight, BMI, FPG, FIN, HOMA-IR, SBP, AD and the positive pathological biopsy rate, and the positive pathological biopsy rate was significantly correlated with weight, BMI, HOMA-IR, SBP, AD and BIRADS grade. The logistic regression analysis revealed that the BIRADS grade was significantly correlated with the positive pathological biopsy rate and AD and that the positive pathological biopsy rate was significantly correlated with the BIRADS grade.Conclusion: As adjunctive therapy, the combination of lifestyle changes and metformin was found to be a safe strategy for improving related metabolic markers and increasing adiponectin. The BIRADS grade was significantly correlated with the positive pathological biopsy rate and AD, and the positive pathological biopsy rate was significantly correlated with the BIRADS grade.Keywords: metformin, breast density, overweight/obese, adiponectin

Ran Chen,1,&ast; Tingting Wang,2,&ast; Jie Song,1,&ast; Daojun Pu,3,&ast; Dan He,1 Jianjun Li,1 Jie Yang,1 Kailing Li,1 Cailing Zhong,1 Jingqing Zhang1 1Chongqing Research Center for Pharmaceutical Engineering, School of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Biochemistry and Molecular Biology Laboratory, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Pharmaceutical Institute, Southwest Pharmaceutical Limited Company, Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingqing Zhang Email zjqrae01@163.comAbstract: Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 (COVID-19). Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.Keywords: antiviral drug, delivery systems, metabolism, pharmacokinetics, pharmacodynamics

Wencheng Ding,1,* Teng Ji,1,* Wei Xiong,2 Tian Li,1 Demin Pu,1 Rong Liu1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Pharmacology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Purpose: In this study, we investigated the effect of Realgar on the apoptosis of HPV16-positive cervical cells in vitro. Methods: The effect of Realgar on the apoptosis of HPV16-positive cervical cells was investigated by annexin V-fluorescein isothiocyanate/propidium iodide staining and growth inhibition assays using HPV16-positive cervical cancer cell line SiHa and HPV16-positive immortalized cervical epithelial cell line S12. The expression of genes was measured by real-time PCR, and the expression of corresponding proteins was detected by Western blotting. The adhesion and invasion of cells were detected by adhesion assay and Transwell invasion assay, respectively. Results: The Realgar inhibited the proliferation and induced the apoptosis of SiHa and S12 cells in a dose- and time-dependent manner. The Realgar suppressed the expression of HPV16 E7 and caspase-3. The Realgar suppressed the adhesion and invasion of both cells. Conclusion: The Realgar induced apoptosis, inhibited the proliferation of HPV16-positive cell lines through a HPV16 E7-dependent pathway, and inhibited cell adhesion and invasion. Keywords: Realgar, antitumor, human papillomavirus, E7

Abstract Background The best antiviral treatment for chronic hepatitis B (CHB) poses a complex challenge. The treatment effect of the combination of nucleoside analogues (NAs) and pegylated interferon alpha (PegIFN) was still in debate. Methods We studied patients treated with NAs and PegIFN-2b at our institution from November 2019 to January 2022. Logistic regression identified independent factors influencing clinical cure. The predictive accuracy of the formula was assessed using the Receiver operating characteristic (ROC) curve at different time points (before therapy, 12 weeks, and 24 weeks into treatment). Results A total of 120 patients were enrolled in the final analysis. Among the cohort of patients under study, 71 (59.1%) patients had clinical cure while 49 (40.9%) patients did not. Hepatitis B surface antigen (HBsAg) at baseline and age were the powerful variables predicting the clearance of HBsAg. The area under the ROC (AUC) was 0.907 for pre-treatment predictive model, 0.958 for 12-week predictive model and 0.747 for 24-week predictive model. Conclusion This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy. Future research that explores additional factors, such as HBV genotype, in a larger cohort study is needed.

Abstract Background Hearing loss (HL) is the most common sensory birth deficit worldwide, with causative variants in more than 150 genes. However, the etiological contribution and clinical manifestations of X-linked inheritance in HL remain unclear within the Chinese HL population. In this study, we focused on X-linked hereditary HL and aimed to assess its contribution to hereditary HL and identify the genotype–phenotype relationship. Methods We performed a molecular epidemiological investigation of X-linked hereditary HL based on next-generation sequencing and third-generation sequencing in 3646 unrelated patients with HL. We also discussed the clinical features associated with X-linked non-syndromic HL-related genes based on a review of the literature. Results We obtained a diagnostic rate of 52.72% (1922/3646) among our patients; the aggregate contribution of HL caused by genes on the X chromosome in this cohort was ~ 1.14% (22/1922), and POU3F4 variants caused ~ 59% (13/22) of these cases. We found that X-linked HL was congenital or began during childhood in all cases, with representative audiological profiles or typical cochlear malformations in certain genes. Genotypic and phenotypic analyses showed that causative variants in PRPS1 and AIFM1 were mainly of the missense type, suggesting that phenotypic variability was correlated with the different effects that the replaced residues exert on structure and function. Variations in SMPX causing truncation of the protein product were associated with DFNX4, which resulted in typical audiological profiles before and after the age of 10 years, whereas nontruncated proteins typically led to distal myopathy. No phenotypic differences were identified in patients carrying POU3F4 or COL4A6 variants. Conclusions Our work constitutes a preliminary evaluation of the molecular contribution of X-linked genes in heritable HL (~ 1.14%). The 15 novel variants reported here expand the mutational spectrum of these genes. Analysis of the genotype–phenotype relationship is valuable for X-linked HL precise diagnostics and genetic counseling. Elucidation of the pathogenic mechanisms and audiological profiles of HL can also guide choices regarding treatment modalities.

Objective To investigate the effects of circ_UBE2C on the proliferation and glycolysis of lung cancer cells and its mechanism of action. Methods The expression of circ_UBE2C, miR-107, and hexokinase 2 (HK2) in lung cancer tissues and normal lung tissues were analyzed based on the The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival curve was plotted to analyze the correlation between circ_UBE2C/miR-107/HK2 expression and survival of the lung cancer patients. qRT-PCR was used to detect the expression of circ_UBE2C and miR-107, and Western blotting was employed to measure the expression of HK2 and PCNA in human normal lung epithelial cells (BEAS-2B) and human lung cancer cell lines (A549, NCI-H460, and NCI-H1299). Then A549 and NCI-H1299 cells were divided into the blank group (NC), circ_UBE2C knockdown group (si-circ), HK2 knockdown group (si-HK2), simultaneous knockdown of miR-107+HK2 group (miR-inhibitor+si-HK2), and simultaneous knockdown of circ_UBE2C+miR-107 group (si-circ+miR-inhibitor). CCK-8 assay and colony formation assay were employed to measure the proliferation of above cell groups. The glucose uptake, lactate generation, and ATP production in the cells were measured by glucose uptake colorimetric assay kit, lactic acid detection kit, and ATP content determination kit, respectively. Seahorse XF glycolytic stress test and Seahorse XF cellular mitochondrial stress test were respectively performed to detect the extracellular acidification ratio (ECAR) and cellular oxygen consumption ratio (OCR). The targeting relationship between the circ_UBE2C and miR-107, and miR-107 and HK2 was validated by dual-luciferase reporter gene assay. Results Compared with normal lung tissues, the expression of circ_UBE2C and HK2 was up-regulated, while that of miR-107 was down-regulated in lung cancer tissues (P < 0.05). The expression of circ_UBE2C and HK2 was elevated, and that of miR-107 was reduced in A549 and NCI-H1299 cells when compared with BEAS-2B cells (P < 0.05). Survival analysis showed that the patients with high expression of circ_UBE2C and HK2 or low expression of miR-107 had shorter survival (P < 0.05). Compared with the NC group, both si-circ and si-HK2 resulted in significantly reduced proliferation, glucose uptake, lactate generation, ATP production, and ECAR and OCR values in A549 and NCI-H1299 cells (P < 0.05). Dual luciferase reporter gene assay confirmed that circ_UBE2C could directly bind to and negatively regulate miR-107 expression. HK2 was then identified as a downstream target of miR-107. Compared with the si-HK2 group, the proliferative ability and glycolysis level of A549 and NCI-H1299 cells were significantly increased in the miR-inhibitor+si-HK2 group and the si-circ+miR-inhibitor group. Conclusion Knockdown of circ_UBE2C significantly suppresses the proliferation and glycolysis of lung cancer cells via targeting up-regulation of miR-107 and then exerting inhibitory effect on HK2 expression.

As an emerging joint learning model, federated learning is a promising way to combine model parameters of different users for training and inference without collecting users’ original data. However, a practical and efficient solution has not been established in previous work due to the absence of efficient matrix computation and cryptography schemes in the privacy-preserving federated learning model, especially in partially homomorphic cryptosystems. In this paper, we propose a Practical and Efficient Privacy-preserving Federated Learning (PEPFL) framework. First, we present a lifted distributed ElGamal cryptosystem for federated learning, which can solve the multi-key problem in federated learning. Secondly, we develop a Practical Partially Single Instruction Multiple Data (PSIMD) parallelism scheme that can encode a plaintext matrix into single plaintext for encryption, improving the encryption efficiency and reducing the communication cost in partially homomorphic cryptosystem. In addition, based on the Convolutional Neural Network (CNN) and the designed cryptosystem, a novel privacy-preserving federated learning framework is designed by using Momentum Gradient Descent (MGD). Finally, we evaluate the security and performance of PEPFL. The experiment results demonstrate that the scheme is practicable, effective, and secure with low communication and computation costs.

Background: Parkinson's disease non-motor symptoms (PD-NMS) significantly affect patients' quality of life. Acupuncture has emerged as a potential complementary therapy for PD-NMS. This study aims to investigate general research status, hotspots and trends of acupuncture as a treatment for PD-NMS. Methods: Literature on Web of Science Core Collection (WoSCC) from 2003 to 2023 was retrieved, and bibliometric analysis was conducted using VOSviewer and CiteSpace software. Results: 159 publications by 894 authors from 37 countries, 300 institutions, and 96 journals were retrieved and analyzed. The number of publications in this field is generally on the rise yearly. China was the leading contributor with 57 publications, and the United States followed with 36 publications and had the highest total citation count of 1562. Guangzhou University of Chinese Medicine ranked the highest with a total of 12 publications, while Harvard University had the highest average citation rate of 70 citations per publication. Evidence-Based Complementary and Alternative Medicine was the most prolific journal with 11 articles that had accumulated 122 citations. Park Hi-Joon was the leading contributor with seven articles and 314 citations. The keyword analysis highlighted emerging areas of interest like “deep brain stimulation” and “alpha-synuclein”. Conclusion: Different countries, institutions, and authors should enhance cooperations, and the underlying mechanisms of acupuncture for PD-NMS should be demonstrated. This study will be helpful for better understanding the current knowledge and gaps in the areas of acupuncture as a treatment of PD-NMS.

This paper introduces a new prefabricated recyclable double-row piles retaining system for excavations in silty clay ground. Laboratory model test and numerical simulation are conducted to study the system behavior upon excavation. The horizontal displacement (δh), Von Mises stress (σM), strain (ε), ground surface settlement (δv), and earth pressure are systematically investigated. Furthermore, the monitoring data of 13 excavation cases supported by double-row piles retaining system are presented and discussed. The experimental results can basically match the numerical results, and the maximum σM, maximum bending moment (Mmax), maximum horizontal displacement (δhm) of structural members are all less than the tolerance limits. The ground surface settlement model of double-row piles retaining system consists of three zones, i.e., rebound influence zone, primary influence zone and secondary influence zone. The δhm values are 0.07%–1.42% of the excavation depth (He). The maximum ground surface settlement (δvm) is generally less than δhm. The ratio of δvm/δhm varies between 0.09 and 0.76, with an average value of 0.5. The observed earth pressure on the retained side of front pile (paf) is about 0.53–0.57 γH below the excavation surface. Above the excavation surface, paf decreases dramatically when getting closer to the ground surface.

This study addresses the issue of unsatisfactory smoothness in the movement of integrated internal and external cross roller bearings post-assembly, which compromises the movement flexibility of the finished bearing and fails to meet index requirements. Focusing on a specific type of precision cross roller bearing, this paper establishes a finite element explicit dynamic simulation model that takes into account the plugging position and matching relationship. A transient dynamic simulation of the roller blockage process was conducted, yielding insights into the contact pressure and deformation experienced by the roller and plug during this blockage. The results indicate that when both the taper pin are positioned centrally, and the plug matching clearance, plug sag and protruding amount, and plug rotation offset degrees are all set to 0 μm, the contact pressure between the roller and raceway, as well as the roller deformation displacement, are minimized. The plugging position and fit were subsequently validated through testing, which also measured the impact of these parameters on the roundness of the raceway surface and the bearing’s friction torque. The test findings corroborate that when the taper and pin are centrally aligned, and the stopper clearance is 5 μm, with the plug sag, protrusion, and offset all at 0 μm, the roundness of the raceway surface and the bearing’s friction torque reach their lowest values, thereby optimizing the stability of bearing motion. By comparing the simulation and experimental results, it is concluded that during bearing assembly, it is crucial to maintain the taper pin in a central position, control the plug matching clearance to approximately 5 μm, and ensure the plug sag, protrusion, and rotation offset amount are both at 0 μm. This approach guarantees optimal contact conditions and motion stability during operation. The findings of this research offer valuable design guidance for the selection of appropriate plugging positions and fits in precision cross roller bearings.

Mitochondrial transfer RNA mutation is one of the most important causes of hereditary hearing loss in humans. Mitochondrial transfer RNASer (UCN) gene is another hot spot for mutations associated with non-syndromic hearing loss, besides the 12S ribosomal RNA gene. In this study, we assessed the clinical phenotype and the molecular characteristics of two Chinese families with non-syndromic hearing loss. Mutational analysis revealed that 7445A > G and 7510T > C mutations in the mitochondrial transfer RNASer (UCN) gene were the molecular etiology of Family 1 and Family 2, respectively. However, the clinical and genetic characteristics of the two families carrying the above mutations in the transfer RNASer (UCN) gene exhibited a variable expression of hearing loss and an incomplete penetrance. Sequencing analysis of the complete mitochondrial genome showed the presence of transfer RNATrp 5568A > G and NADH-ubiquinone oxidoreductase chain 4 11696G > A mutations in Family 1. The mitochondrial haplotype analysis showed that the two families belonged to Asian D4 and M80′D haplotypes, respectively, and no pathogenic variations were found in the nuclear genes. To our knowledge, our study is the first to report 7445A > G and 7510T > C mutations in the mitochondrial transfer RNASer (UCN) gene, in multi-generation non-syndromic hearing loss pedigrees from China. Our study suggests that 5568A > G and 11696G > A mutations may enhance the penetrance of hearing loss in Chinese Family 1, while mitochondrial haplotypes and known nuclear genes may not be modifiers for the phenotypic expression of 7445A > G and 7510T > C mutations in these Chinese families.

The stability and high quality of electricity are the basic factors which ensure that the residents and enterprises lead a happy and productive life. Therefore, in order to meet the requirements of residents’ life and enterprise production, it is necessary to improve the efficiency and accuracy of power grid fault diagnosis. In this paper, the knowledge graph is integrated into the power grid fault diagnosis, and the fault diagnosis system of the knowledge graph is constructed to realise the fault diagnosis of the power grid. The article first completes the knowledge graph construction through knowledge extraction, knowledge fusion and knowledge processing; then, it completes the construction of the fault scheduling knowledge graph through power grid equipment fault records, entity attribute extraction, coreference resolution, relation extraction, relation screening and data integration; finally, combined with the fault information knowledge analysis technology, it builds a power grid fault diagnosis system using a knowledge graph. Experiments show that using the system to diagnose the fault quantity, fault location and fault analysis information of the pilot power grid not only has ideal efficiency but also has high accuracy.

With the rapid increase in computer users’ requirements for image information and image processing, and the rapid development of the intelligent process, the ability of the traditional visual system to process image information and data has been difficult to meet the needs of users. Therefore, in this article, we upgrade the vision system of smart cameras by introducing three network algorithm structures: convolutional neural network (CNN), LSTM and CNN-LSTM. We compare the classification performance of the three algorithms and evaluate them with three metrics: accuracy, precision and recall. The experimental results show that using the CNN algorithm, the accuracy of image information processing is 98.2%, the precision can reach 87.5% and the recall rate is 99.8%; the LSTM accuracy is 97.7%, its precision is 89.6% and its recall rate is 87.3%; its precision can be improved to 90.5% and the recall rate to 99.7%.

Abstract Background Biological laboratories and companies involved in antibody development need convenient and versatile methods to detect highly active antibodies. Methods To develop a mammalian cell-based ZZ display system for antibody quantification, the eukaryotic ZZ-displayed plasmid was constructed and transfected into CHO cells. After screening by flow cytometric sorting, the stable ZZ display cells were incubated with reference IgG and samples with unknown IgG content for 40 min at 4℃, the relative fluorescence intensity of cells was analyzed and the concentration of IgG was calculated. Results By investigating the effects of different display-associated genetic elements, a eukaryotic ZZ-displaying plasmid with the highest display efficiency were constructed. After transfection and screening, almost 100% of the cells were able to display the ZZ peptide (designated CHO-ZZ cells). These stable CHO-ZZ cells were able to capture a variety of IgG, including human, rabbit, donkey and even mouse and goat. CHO-ZZ cells could be used to quantify human IgG in the range of approximately 12.5–1000 ng/mL, and to identify high-yielding engineered monoclonal cell lines. Conclusions We have established a highly efficient CHO-ZZ display system in this study, which enables the quantification of IgG from various species under physiological conditions. This system offers the advantage of eliminating the need for antibody purification and will contribute to antibody development.

Abstract Background Iatrogenic facial nerve injury is one of the severest complications of middle ear surgery, this study aims to evaluate surgical management and prognosis in the era of improved surgical instruments. Methods Patients suffered from facial nerve paralysis after middle ear surgery between January 2000 and December 2019 were retrospectively collected. Demographic characters, primary disease and surgery, details of revision surgery were analyzed. Results Forty-five patients were collected, of whom 8 were injured at our center and 37 were transferred. For 8 patients injured at our center, seven (87.5%) ranked House-Brackmann (H-B) grade V and one (12.5%) ranked H-B VI before revision surgery; postoperatively, two (25.0%) patients recovered to H-B grade I, four (50.0%) recovered to H-B II, and the other two (25.0%) recovered to H-B III. For 37 patients transferred, thirteen (35.1%) ranked H-B grade V and 24 (64.9%) ranked H-B VI preoperatively, final postoperative grade ranked from H-B grade I to grade V, with H-B I 6 (16.2%) cases, H-B II 6 (16.2%) cases, H-B III 18 (48.6%) cases, H-B IV 5 (13.5%) cases and H-B V 2 (5.4%) cases. The most vulnerable site was tympanic segment (5, 62.5% and 27, 73.0% respectively). Twenty-one (46.7%) patients suffered from mild injury and 24 (53.3%) suffered from partial or complete nerve transection. For surgical management, twenty-one (46.7%) patients received decompression, nineteen (42.2%) received graft and 5 (11.1%) received anastomosis. Those decompressed within 2 months after paralysis had higher possibility of H-B grade I or II recovery (P = 0.026), those received graft within 6 months were more likely to get H-B grade III recovery (P = 0.041), and for patients underwent anastomosis within 6 months, all recovered to H-B grade III. Conclusions Tympanic segment is the vulnerable site. If facial nerve paralysis happens, high-resolution computed tomography could help identify the injured site. Timely treatment is important, decompression within 2 months after paralysis, graft and anastomosis within 6 months lead to better recovery.

Abstract The intrinsically disordered protein tau aggregates into β-sheet amyloid fibrils that spread in human brains afflicted with Alzheimer’s disease and other neurodegenerative diseases. Tau interaction with lipid membranes might play a role in the formation and spreading of these pathological aggregates. Here we investigate the conformation and assembly of membrane-induced tau aggregates using solid-state NMR and transmission electron microscopy. A tau construct that encompasses the microtubule-binding repeats and a proline-rich domain is reconstituted into cholesterol-containing phospholipid membranes. 2D 13C-13C correlation spectra indicate that tau converted from a random coil to a β-sheet conformation over weeks. Small unilamellar vesicles (SUVs) cause different equilibrium conformations from large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). Importantly, SUV-bound tau developed long fibrils that exhibit the characteristic β-sheet chemical shifts of Tyr310 in heparin-fibrillized tau. In comparison, LUVs and MLVs do not induce fibrils but cause different β-sheet aggregates. Lipid-protein correlation spectra indicate that these tau aggregates reside at the membrane-water interface, without inserting into the middle of the lipid bilayer. Removal of cholesterol from the SUVs abolished the fibrils, indicating that both membrane curvature and cholesterol are required for tau fibril formation. These results have implications for how lipid membranes might nucleate tau aggregates.

Aiming at the difficulty of analyzing the meshing contact characteristics of gear transmission system under the big data formed by multiple working conditions and uncertain parameters, a meshing contact characteristics analysis method of gear transmission system based on data mining technology is proposed. Based on the principle of multi-dimensional Gaussian distribution and the finite element model of gear transmission system, the meshing contact characteristic data set of the system is constructed. The correlation between system parameters and meshing contact characteristics is analyzed using the maximum information coefficient, which provides a candidate feature subset for the prediction model. Then, the prediction model of meshing contact characteristics of the system is established using support vector machine and random forest algorithm, which realizes the efficient prediction of meshing contact characteristics of the system. The results show that the prediction error of the prediction model based on support vector machine is the smallest, and the average absolute percentage error is 3.87%, which is far less than the theoretical calculation error. Under the optimal feature subset, the prediction error index of contact characteristics of the prediction model based on support vector machine decreases significantly, and its average absolute percentage error reaches 3.03%, which is 21.71% lower than the prediction error of contact characteristics before optimization. These have verified the accuracy and effectiveness of the proposed method.

BackgroundCochlear implantation (CI) outcomes in patients with auditory neuropathy (AN) are variable, which hampers patients’ decisions on CI.ObjectiveThis study aims to assess the outcomes of CI in individuals diagnosed with AN and to examine the various factors that may influence the effectiveness of this intervention.MethodsA total of 75 patients diagnosed with AN were included in the study. The hearing threshold, the score of categories of auditory performance (CAP), speech intelligibility rating (SIR), and speech audiometry were tested. Genetic testing was conducted by medical exome sequencing in 46 patients.ResultsAfter CI, the average aided hearing threshold for patients with prelingual and post-lingual onset was 38.25 ± 6.63 dB and 32.58 ± 9.26 dB, respectively; CAP score improved to 5.52 ± 1.64 (p

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Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture. [ABSTRACT FROM AUTHOR]

Abstract Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants.

Over the past three decades, multiple reverberation mapping (RM) campaigns conducted for the quasar PG 2130+099 have exhibited inconsistent findings with time delays ranging from ∼10 to ∼200 days. To achieve a comprehensive understanding of the geometry and dynamics of the broad-line region (BLR) in PG 2130+099, we continued an ongoing high-cadence RM monitoring campaign using the Calar Alto Observatory 2.2 m optical telescope for an extra four years from 2019 to 2022. We measured the time lags of several broad emission lines (including He ii , He i , H β , and Fe ii ) with respect to the 5100 Å continuum, and their time lags continuously vary through the years. Especially, the H β time lags exhibited approximately a factor of 2 increase in the last two years. Additionally, the velocity-resolved time delays of the broad H β emission line reveal a back-and-forth change between signs of virial motion and inflow in the BLR. The combination of negligible (∼10%) continuum change and substantial time-lag variation (over 2 times) results in a significant scatter in the intrinsic R _H _β – L _5100 relationship for PG 2130+099. Taking the consistent changes in the continuum variability time scale and the size of the BLR into account, we tentatively propose that the changes in the measurement of the BLR size may be affected by “geometric dilution”

We conduct a reverberation mapping (RM) campaign to spectroscopically monitor a sample of selected bright active galactic nuclei with large anticipated broad-line region (BLR) sizes adequate for spectroastrometric (SA) observations by the GRAVITY instrument on the Very Large Telescope Interferometer. We report the first results for five objects, IC 4329A, Mrk 335, Mrk 509, Mrk 1239, and PDS 456, among which Mrk 1239 and PDS 456 are for the first time spectroscopically monitored. We obtain multiyear monitoring data and perform multicomponent spectral decomposition to extract the broad H β profiles. We detect significant time lags between the H β and continuum variations, generally obeying the previously established BLR size–luminosity relation. Velocity-resolved H β time lags illustrate diverse, possibly evolving, BLR kinematics. We further measure the H β line widths from mean and rms spectra and the resulting virial products show good consistency among different observing seasons. Adopting a unity virial factor and the FWHM of the broad H β line from the mean spectra as a measure of velocity, the obtained black hole masses averaged over seasons are $\mathrm{log}{M}_{\bullet }/{M}_{\odot }={8.02}_{-0.14}^{+0.09}$ , ${6.92}_{-0.12}^{+0.12}$ , ${8.01}_{-0.25}^{+0.16}$ , ${7.44}_{-0.14}^{+0.13}$ , and ${8.59}_{-0.11}^{+0.07}$ for the five objects, respectively. Black hole mass estimations using other line width measures are also reported. For objects with previous RM campaigns, our mass estimates are in agreement with earlier results. In a companion paper, we will employ BLR dynamical modeling to directly infer the black hole mass and thereby determine the virial factors.

Reverberation mapping (RM) has long been a powerful tool for measuring the masses of supermassive black holes (SMBHs) at the centers of active galactic nuclei (AGNs), but the precision of these mass measurements depends on the so-called virial factors. It has been demonstrated that the virial factors exhibit significant diversity, spanning approximately 1–2 orders of magnitude across different AGNs. However, the underlying physical drivers for the diversity have not yet been finalized. Here, adopting the SMBH mass–spheroid luminosity relations of inactive galaxies with different bulge classifications, we calibrate the virial factors corresponding to the AGNs with pseudobulges (PBs) and classical bulges (or elliptical hosts, CBs) using the latest nearby RM sample. We investigate the correlations between virial factors and the AGN spectral properties, and find that for both PB and CB samples, the FWHM-based virial factors exhibit significant anticorrelations with the emission-line widths and profiles, while the σ _line -based virial factors only show moderate anticorrelations with line widths for PBs. We attribute these correlations mainly to the inclination angle or opening angle of the broad-line regions. Moreover, we establish new relations to give more precise virial factors and, in combination with the latest iron-corrected radius–luminosity relation, tentatively develop new single-epoch estimators of SMBH masses, which enable more accurate measurements of SMBH masses in large AGN samples.