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Objective: To investigate the depersonalization status and to analyze the effect of workplace incivility perception, intrusive rumination and fear of negative evaluation on depersonalization in clinical nurses. Methods: In May 2019, 10 cities were selected as sampling cities by the method of grabbing random ball in Henan Province and Fujian Province. Using the stratified sampling, clinical nurses were selected as the research objects for a questionnaire survey in 22 tertiary hospitals and 23 secondary hospitals, included 1200 nurses. A total of 1200 questionnaires were issued and collected, and 1159 valid questionnaires were collected with effective recovery of 96.6%. Clinical nurses were investigated by Workplace Incivility Scale, Event Related Rumination Inventory, Fear of Negative Evaluation Scale, Maslach Burnout Inventory-General Survey. The demographic characteristics of nurses' depersonalization were compared and analyzed with t test and single factor analysis of variance. The influence mechanism of workplace incivility perception, intrusive rumination and fear of negative evaluation on depersonalization was analyzed with Bootstrap. Results: Depersonalization scores were (9.3±2.6) points, 467 of those had depersonalization symptoms in clinical nurses (40.3%). The scores of depersonalization of those with <3 years of service [ (10.5±2.9) points] was higher than those with 3-10 years [ (9.1±2.8) points] and 11-31 years [ (9.0±2.9) points]. The scores of depersonalization of those with monthly earning of <3000 yuan [ (10.1±2.8) points] was higher than those with 3000-7999 yuan [ (8.4±2.7) points] and 8000-12000 yuan [ (8.0±2.9) points]. The scores of depersonalization of clinical nurses in surgical departments [ (10.0±2.9) points] was higher than those in non-surgical departments [ (8.7±2.6) points]. The scores of depersonalization of clinical nurses in tertiary hospitals [ (10.0±2.7) points] was higher than those in secondary hospitals [ (8.6±2.8) points]. The differences were statistically significant ( P <0.05). Workplace incivility perception affected depersonalization through the single mediating role of intrusive rumination, fear of negative evaluation and the chain mediating role of intrusive rumination and fear of negative evaluation ( β =0.16, 0.17, 0.07, 95% CI : 0.15-0.20, 0.15-0.21, 0.03-0.09, P <0.05) . Conclusion: Workplace incivility perception directly or through the independent mediating effects of intrusive rumination or fear of negative evaluation, and the chain mediating effects of intrusive rumination and fear of negative evaluation influences the depersonalization of clinical nurses.

Background: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis., Aim: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM., Methods: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed., Results: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis., Conclusion: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1 , S E S A M 2 , and S E S A M 3 , respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 10 14 / c m 2 . The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of V ss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (C max ) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

Introduction: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics., Methods: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately., Results: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect., Conclusions: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Study Objectives: We examined body mass index (BMI) changes associated with sodium oxybate treatment (SXB) in pediatric patients with narcolepsy with cataplexy who participated in a double-blind, placebo-controlled, randomized withdrawal study and an open-label continuation period., Methods: Participants were aged 7-16 years at screening. SXB-naive participants titrated to twice-nightly dosing of SXB then entered a 2-week stable-dose period; participants taking SXB at study entry entered a 3-week stable-dose period. After a 2-week randomized withdrawal period, all participants entered an open-label safety period (OLP; main study duration: ≤ 52 weeks). Participants who completed the OLP were allowed to enter the open-label continuation period (an additional 1-2 years). BMI percentile categories were defined as underweight (< 5th), normal (5th to < 85th), overweight (≥ 85th to < 95th), and obese (≥ 95th)., Results: Median BMI percentile decreased from baseline to OLP week 52 in SXB-naive participants who were normal weight at baseline (decreased from 77.0 to 35.0) or overweight/obese at baseline (98.0 to 86.7). Median BMI percentile decreased to a lesser extent in participants taking twice-nightly SXB at study entry who were normal weight at baseline (54.6 to 53.0) or overweight/obese at baseline (96.5 to 88.9). Shifts in BMI category from baseline to week 52 were sometimes noted. In SXB-naive participants, 9/10 (90.0%) who were overweight became normal weight, 7/25 (28.0%) who were obese became normal weight, 3/25 (12.0%) who were obese became overweight, and 1/16 (6.3%) who was normal weight became obese. In participants taking SXB at baseline, 5/8 (62.5%) who were overweight became normal weight, 3/6 (50.0%) who were obese became overweight, 1/14 (7.1%) who was normal weight became overweight, and 2/14 (14.3%) who were normal weight became underweight. Median BMI percentiles at months 6 and 12 of the open-label continuation period were similar to those at OLP end (OLP week 52). In SXB-naive participants, the evident BMI z-score decrease over time was relative to the screening values., Conclusions: Decreases in BMI percentile and z-score, and downward shifts in BMI category, were observed within 1 year of SXB treatment in pediatric participants with narcolepsy with cataplexy. BMI decreases plateaued after approximately 1 year., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: A Multicenter Study of the Efficacy and Safety of Xyrem With an Open-Label Pharmacokinetic Evaluation and Safety Extension in Pediatric Subjects With Narcolepsy With Cataplexy; URL: https://clinicaltrials.gov/study/NCT02221869; Identifier: NCT02221869., Citation: Dauvilliers Y, Lammers GJ, Lecendreux M, et al. Effect of sodium oxybate on body mass index in pediatric patients with narcolepsy. J Clin Sleep Med . 2024;20(3):445-454., (© 2024 American Academy of Sleep Medicine.)

Surface water plays a crucial role in the ecological environment and societal development. Remote sensing detection serves as a significant approach to understand the temporal and spatial change in surface water series (SWS) and to directly construct long-term SWS. Limited by various factors such as cloud, cloud shadow, and problematic satellite sensor monitoring, the existent surface water mapping datasets might be short and incomplete due to losing raw information on certain dates. Improved algorithms are desired to increase the completeness and quality of SWS datasets. The present study proposes an automated framework to detect SWS, based on the Google Earth Engine and Landsat satellite imagery. This framework incorporates implementing a raw image filtering algorithm to increase available images, thereby expanding the completeness. It improves OTSU thresholding by replacing anomaly thresholds with the median value, thus enhancing the accuracy of SWS datasets. Gaps caused by Landsat7 ETM + SLC-off are respired with the random forest algorithm and morphological operations. The results show that this novel framework effectively expands the long-term series of SWS for three surface water bodies with distinct geomorphological patterns. The evaluation of confusion matrices suggests the good performance of extracting surface water, with the overall accuracy ranging from 0.96 to 0.97, and user's accuracy between 0.96 and 0.98, producer's accuracy ranging from 0.83 to 0.89, and Matthews correlation coefficient ranging from 0.87 to 0.9 for several spectral water indices (NDWI, MNDWI, ANNDWI, and AWEI). Compared with the Global Reservoirs Surface Area Dynamics (GRSAD) dataset, our constructed datasets promote greater completeness of SWS datasets by 27.01%-91.89% for the selected water bodies. The proposed framework for detecting SWS shows good potential in enlarging and completing long-term global-scale SWS datasets, capable of supporting assessments of surface-water-related environmental management and disaster prevention., Competing Interests: Declaration of competing interest We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. This study has no conflicts of interest to other bodies., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To understand the infection status and molecular types of rhinovirus (RV) among cases of Acute Respiratory Infections (ARIs) in Luohe City, Henan Province, from 2017 to 2022. Methods: From October 2017 to June 2022, clinical and epidemiological data were collected from 2 270 cases of ARIs at Luohe Central Hospital in Henan Province. Throat swab specimens were obtained from these cases. Real-time quantitative polymerase chain reaction (qPCR) was used to screen for RV-positive specimens. Subsequently, the positive samples were subjected to nested reverse transcription polymerase chain reaction (nested RT-PCR) to amplify the full-length VP1 region. Using the MEGA software, along with 169 RV reference strains recommended by the International Committee on Taxonomy of Viruses, a phylogenetic tree was constructed to determine RV types. Results: Among the 2 270 cases of ARIs, there were 1 283 male cases (56.52%). The median age ( Q 1 , Q 3 ) was 3 (1, 6) years, with the population under 5 years old accounting for 68.59% (1 557/2 270). RV was detected in 137 cases (6.04%), of which 68 cases (49.64%) showed co-detection with other viruses, with the most common being co-detection with enterovirus, accounting for 14.60% (20/137). The RV detection rates in the age groups of 0~4 years, 5~14 years, 15~59 years, and≥60 years were 6.42% (100/1 557), 4.69% (21/448), 3.80% (6/158), and 9.35% (10/107), respectively, with no statistically significant differences ( χ 2 =5.310, P =0.150). The overall detection rates of RV before (2017-2019) and during (2020-2022) the COVID-19 pandemic showed no statistically significant difference ( χ 2 =1.823, P =0.177). A total of 109 VP1 sequences were obtained, including 62 types. Among them, RV-A, RV-B, and RV-C had 42, 3, and 17 types respectively. Conclusion: RV is one of the predominant pathogens in ARIs cases in Luohe City, Henan Province, from 2017 to 2022. Multiple types of RV co-circulate without any apparent dominant type.

The catalytic hydrogenation of biomass-derived chemicals is essential in chemical industry due to the growing demand for sustainable and renewable energy sources. In this study, we present a comprehensive theoretical investigation regarding the hydrogenation of glycolaldehyde to ethylene glycol over a Ru/C catalyst by employing density functional theory and ab initio molecular dynamics simulations. With inclusion of explicit solvation, we have demonstrated that the glycolaldehyde hydrogenation is significantly improved due to the fast proton transfer through the hydrogen bond network. The enhanced activity could be attributed to the participation of the solvent water as the hydrogen source and the highly positively charged state of a Ru cluster in an aqueous phase, which are critical for the activation of aldehyde groups and proton-assisted hydrogenation. Overall, our findings provide valuable insights into glycolaldehyde hydrogenation over Ru/C catalysts in the aqueous phase, highlighting the importance of solvation effects in the biomass conversion., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

In this work, we advanced an efficient free energy sampling method based on constrained ab initio molecular dynamics (cAIMD) with a fully explicit solvent layer to depict the electrochemical reaction process at constant surface charge density, named the "Constant-Potential Thermodynamic Integration (CPTI)" method. For automatically adjusting surface charge density at different states, we built an "on-the-fly" procedure which is capable of managing all the necessary steps during cAIMD simulations, including the system pre-equilibrium, surface charge density updating, and force sampling. We applied it to predict the potential-dependent free energy profiles of CO 2 adsorption on a single-atom catalyst. The results show that our method can not only account for changes in electrostatic potential energy associated with potential but also consider the potential-induced solvation effects. Our approach enables the accurate simulation of electrochemical environment by presenting the complete solid-liquid interface and efficient computation of electrocatalytic reaction energetics based on a robust potential descriptor.

ConspectusSingle atom electrocatalysts, with noble metal-free composition, maximal atom efficiency, and exceptional reactivity toward various energy and environmental applications, have become a research hot spot in the recent decade. Their simplicity and the isolated nature of the atomic structure of their active site have also made them an ideal model catalyst system for studying reaction mechanisms and activity trends. However, the state of the single atom active sites during electrochemical reactions may not be as simple as is usually assumed. To the contrary, the single atom electrocatalysts have been reported to be under greater influence from interfacial dynamics, with solvent and electrolyte ions perpetually interacting with the electrified active center under an applied electrode potential. These complexities render the activity trends and reaction mechanisms derived from simplistic models dubious.In this Account, with a few popular single atom electrocatalysis systems, we show how the change in electrochemical potential induces nontrivial variation in the free energy profile of elemental electrochemical reaction steps, demonstrate how the active centers with different electronic structure features can induce different solvation structures at the interface even for the same reaction intermediate of the simplest electrochemical reaction, and discuss the implication of the complexities on the kinetics and thermodynamics of the reaction system to better address the activity and selectivity trends. We also venture into more intriguing interfacial phenomena, such as alternative reaction pathways and intermediates that are favored and stabilized by solvation and polarization effects, long-range interfacial dynamics across the region far beyond the contact layer, and the dynamic activation or deactivation of single atom sites under operation conditions. We show the necessity of including realistic aspects (explicit solvent, electrolyte, and electrode potential) into the model to correctly capture the physics and chemistry at the electrochemical interface and to understand the reaction mechanisms and reactivity trends. We also demonstrate how the popular simplistic design principles fail and how they can be revised by including the kinetics and interfacial factors in the model. All of these rich dynamics and chemistry would remain hidden or overlooked otherwise. We believe that the complexity at an electrochemical interface is not a curse but a blessing in that it enables deeper understanding and finer control of the potential-dependent free energy landscape of electrochemical reactions, which opens up new dimensions for further design and optimization of single atom electrocatalysts and beyond. Limitations of current methods and challenges faced by the theoretical and experimental communities are discussed, along with the possible solutions awaiting development in the future.

Ethnopharmacological Relevance: Pulmonary fibrosis (PF) is a chronic, progressive, and often fatal interstitial lung disease. Traditional Chinese medicine formulations and their active ingredients have shown potential in the treatment of PF. Panax notoginseng saponin (PNS) is extracted from the widely used traditional Chinese medicinal herb Panax notoginseng (Burkill) F. H. Chen, exhibiting therapeutic effects in pulmonary diseases treatment., Aim of the Study: This study aimed to investigate the effects and elucidate possible potential mechanisms of PNS on bleomycin (BLM)-induced PF in rats., Materials and Methods: PF was induced in rats by intratracheal administration of bleomycin (BLM, 5 mg/kg). After disease model induction, the rats were treated with PNS (50, 100, or 200 mg/kg per day) or pirfenidone (PFD, 50 mg/kg per day) for 28 days. Lung function, histopathological changes, collagen deposition, and E- and N-cadherin levels in lung tissue were evaluated. The mechanism of action of PNS was investigated using tandem mass tag-based quantitative proteomics analysis. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were performed to verify the proteomic results., Results: PNS treatment improved lung function, ameliorated the BLM-induced increase in the lung coefficient, attenuated the degree of alveolar inflammation and fibrosis, and reduced the elevated collagen level in PF rats. PNS treatment also down-regulated the expression of N-cadherin while up-regulating the expression of E-cadherin. Proteomic and bioinformatic analyses revealed that the renin-angiotensin system (RAS) was closely related to the therapeutic effect of PNS. Immunohistochemistry, Western blot, and ELISA results indicated that PNS exerted its anti-fibrotic effect via regulation of the balance between the angiotensin-converting enzyme (ACE)-angiotensin (Ang)II-AngII receptor type 1 (AT1R) and ACE2-Ang(1-7)-MasR axes., Conclusions: PNS ameliorates BLM-induced PF in rats by modulating the RAS homeostasis, and is a new potential therapeutic agent for PF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Many person-fit statistics have been proposed to detect aberrant response behaviors (e.g., cheating, guessing). Among them, l z is one of the most widely used indices. The computation of l z assumes the item and person parameters are known. In reality, they often have to be estimated from data. The better the estimation, the better l z will perform. When aberrant behaviors occur, the person and item parameter estimations are inaccurate, which in turn degrade the performance of l z . In this study, an iterative procedure was developed to attain more accurate person parameter estimates for improved performance of l z . A series of simulations were conducted to evaluate the iterative procedure under two conditions of item parameters, known and unknown, and three aberrant response styles of difficulty-sharing cheating, random-sharing cheating, and random guessing. The results demonstrated the superiority of the iterative procedure over the non-iterative one in maintaining control of Type-I error rates and improving the power of detecting aberrant responses. The proposed procedure was applied to a high-stake intelligence test.

The Yarlung Tsangpo River Basin is characterized by its intricate topography and a significant presence of erosive materials. These often coincide with heavy localized precipitation, resulting in pronounced hydraulic erosion and geological hazards in mountainous regions. To tackle this challenge, we integrated the RUSLE-TLSD (Revised Universal Soil Loss Equation-Transportation-limited sediment delivery) model with InSAR (Interferometric Synthetic Aperture Radar) data, aiming to explore the sediment transport process and pinpoint hazard-prone sites within mountainous small watershed. The RUSLE-TLSD model aids in evaluating multi-year sediment transport dynamics in mountainous zones. And, the InSAR data precisely delineates changes in sediment scouring and siltation at sites vulnerable to hazards. Our research estimates that the potential average soil erosion within the watershed stands at 52.33 t/(hm 2 a), with a net soil erosion of 0.69 t/(hm 2 a), the sediment transport pathways manifest within the watershed's gullies and channels. Around 4.32% of the watershed area undergoes sedimentation, predominantly at the base of slopes and within channels. Notably, areas (d) and (e) emerge as the most susceptible to disasters within the watershed. Further analysis of the InSAR data highlighted four regions in the typical area (e) from 2017 that are either sedimentation- or erosion-prone, referred to as "hotspots." Among them, R1 exhibits a strong interplay between water and sediment, rendering it highly sensitive to environmental factors. In contrast, R4, characterized by a sharp bend in siltation, remains relatively impervious to external elements. The NDVI (normalized difference vegetation index) stands out as the pivotal determinant influencing sediment transport within the watershed, exerting a pronounced impact on the outlet section, especially in spring. By employing this approach, we gained a deeper understanding of sediment transport mechanisms and potential hazards in small watershed in uninformative mountainous areas. This study furnishes a robust scientific framework beneficial for erosion mitigation and disaster surveillance in mountainous watersheds., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite the prodigious potential of lithium-sulfur (Li-S) batteries as future rechargeable electrochemical systems, their commercial implementation is hindered by several vital issues, including the shuttle effect and sluggish migration of lithium-polysulfides leading to rapid capacity fading. Here, we systematically investigate the potential of first-row two-dimensional transition metal carbides (TMCs) as sulfur cathodes for Li-S batteries. The adsorption strength of lithium-polysulfides on TMCs is induced by the amount of charge transfer from the former to the latter and the proposed periodic relationship between sulfur in Li 2 S and 3d-transition metals. Our findings show that the VC nanosheet possesses immense anchoring potential and exhibits a comparatively low migration energy barrier for lithium-ion and Li 2 S molecules. Additionally, we report ab initio molecular dynamics simulations for lithiated polysulfide species anchored on a TMC-based model with a liquid-electrolyte medium. The microscopic reaction mechanism, revealed by the evolution of the reaction voltage during lithiation, demonstrates that the dissolution of high-order lithium-polysulfides in the electrolytes can be prevented due to their robust interaction with TMC-based cathode materials. These appealing features suggest that TMCs present colossal performance improvements for anchoring lithium-polysulfides, stimulating the active design of sulfur cathodes for practical Li-S batteries.

Rationale: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF)., Patient Concerns and Diagnoses: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive)., Interventions and Outcomes: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed., Lessons: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Carotid plaque (CP) formation is an important consequence of atherosclerosis and leads to significant complications. Levels of neuropeptide Y (NPY), which is a sympathetic neurotransmitter, are elevated in cardiovascular diseases. It also has important roles in inflammatory conditions. This study aimed to explore the relationship between serum NPY and CP and to study further the influence of NPY and inflammatory factors on CP., Methods: This cross-sectional study was conducted among 300 adults who underwent a health examination at the Second Affiliated Hospital of Fujian Medical University in Fujian Province, of whom 177 were finally enrolled. The participants were divided into the CP (n = 120) and non-CP (NCP) or control (n = 57) groups according to the results of carotid artery color Doppler ultrasound. The CP group was further classified into stable plaque (SP, n = 80) and vulnerable plaque (VP, n = 40) groups based on plaque characteristics. Serum NPY and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) levels were examined. Univariate and correlation analyses were used to evaluate the correlation between serum NPY levels, pro-inflammatory cytokines, and the CP phenotype., Results: The serum NPY and TNF-α levels of patients in the CP group were significantly higher than those in individuals from the NCP group [ (177.30 ± 43.29) pg.mL - 1 vs. (121.53 ± 40.16)pg.mL - 1 , P < 0.001; (41.94 ± 14.19) pg.mL - 1 vs.(33.54 ± 13.37)pg.mL - 1 , P = 0.003]. The serum NPY levels of the patients in the VP group were significantly higher than those in patients from the SP group [(191.67 ± 39.87)ng.L - 1 vs.(170.12 ± 43.37)ng.L - 1 , P = 0.01, P < 0.05]. Serum TNF-α and NPY levels were positively correlated among patients from the CP group (r = 0.184, P = 0.044). The binary logistic regression analysis showed that serum NPY and TNF-α were independent influencing factors of CP [(OR = 1.029, P < 0.001);(OR = 1.030, P = 0.023)]. The area under the ROC curve of NPY predicting the CP showed statistical significance at a value of 0.819., Conclusion: Together, elevated serum NPY levels seem to be associated with the occurrence of coronary atherosclerosis in Chinese adults., (© 2023. The Author(s).)

Aims: The spatiotemporal deep convolutional neural network (DCNN) helps reduce echocardiographic readers' erroneous 'judgement calls' on Takotsubo syndrome (TTS). The aim of this study was to improve the interpretability of the spatiotemporal DCNN to discover latent imaging features associated with causative TTS pathophysiology., Methods and Results: We applied gradient-weighted class activation mapping analysis to visualize an established spatiotemporal DCNN based on the echocardiographic videos to differentiate TTS (150 patients) from anterior wall ST-segment elevation myocardial infarction (STEMI, 150 patients). Forty-eight human expert readers interpreted the same echocardiographic videos and prioritized the regions of interest on myocardium for the differentiation. Based on visualization results, we completed optical flow measurement, myocardial strain, and Doppler/tissue Doppler echocardiography studies to investigate regional myocardial temporal dynamics and diastology. While human readers' visualization predominantly focused on the apex of the heart in TTS patients, the DCNN temporal arm's saliency visualization was attentive on the base of the heart, particularly at the atrioventricular (AV) plane. Compared with STEMI patients, TTS patients consistently showed weaker peak longitudinal displacement (in pixels) in the basal inferoseptal (systolic: 2.15 ± 1.41 vs. 3.10 ± 1.66, P < 0.001; diastolic: 2.36 ± 1.71 vs. 2.97 ± 1.69, P = 0.004) and basal anterolateral (systolic: 2.70 ± 1.96 vs. 3.44 ± 2.13, P = 0.003; diastolic: 2.73 ± 1.70 vs. 3.45 ± 2.20, P = 0.002) segments, and worse longitudinal myocardial strain in the basal inferoseptal (-8.5 ± 3.8% vs. -9.9 ± 4.1%, P = 0.013) and basal anterolateral (-8.6 ± 4.2% vs. -10.4 ± 4.1%, P = 0.006) segments. Meanwhile, TTS patients showed worse diastolic mechanics than STEMI patients (E'/septal: 5.1 ± 1.2 cm/s vs. 6.3 ± 1.5 cm/s, P < 0.001; S'/septal: 5.8 ± 1.3 cm/s vs. 6.8 ± 1.4 cm/s, P < 0.001; E'/lateral: 6.0 ± 1.4 cm/s vs. 7.9 ± 1.6 cm/s, P < 0.001; S'/lateral: 6.3 ± 1.4 cm/s vs. 7.3 ± 1.5 cm/s, P < 0.001; E/E': 15.5 ± 5.6 vs. 12.5 ± 3.5, P < 0.001)., Conclusion: The spatiotemporal DCNN saliency visualization helps identify the pattern of myocardial temporal dynamics and navigates the quantification of regional myocardial mechanics. Reduced AV plane displacement in TTS patients likely correlates with impaired diastolic mechanics., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Delivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.

Background: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit., Methods: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors., Results: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline., Conclusions: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM., (© 2023. The Author(s).)

Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis., Competing Interests: Declaration of competing interest The manuscript has not been published or submitted for publication elsewhere. All of the authors participated in the study and have agreed to the content of the manuscript and declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells., Patients and Methods: We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3)., Results: We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation., Conclusions: TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.

The rational design of electrocatalysis has emerged as one of the most thriving means for mitigating energy and environmental crises. The key to this effort is the understanding of the complex electrochemical interface, wherein the electrode potential as well as various internal factors such as H-bond network, adsorbate coverage, and dynamic behavior of the interface collectively contribute to the electrocatalytic activity and selectivity. In this context, the authors have reviewed recent theoretical advances, and especially, the contributions to modeling the realistic electrocatalytic processes at complex electrochemical interfaces,  and illustrated the challenges and fundamental problems in this field. Specifically, the significance of the inclusion of explicit solvation and electrode potential as well as the strategies toward the design of highly efficient electrocatalysts are discussed. The structure-activity relationships and their dynamic responses to the environment and catalytic functionality under working conditions are illustrated to be crucial factors for understanding the complexed interface and the electrocatalytic activities. It is hoped that this review can help spark new research passion and ultimately bring a step closer to a realistic and systematic modeling method for electrocatalysis., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Graph neural networks (GNNs) have become a popular choice for analyzing graph data in the last few years, and characterizing their expressiveness has become an active area of research. One popular measure of expressiveness is the number of linear regions in neural networks with piecewise linear activations. In this paper, we present estimates for the number of linear regions in classic graph convolutional networks (GCNs) with one layer and multiple-layer scenarios and ReLU activation function. We derive an optimal upper bound for the maximum number of linear regions for one-layer GCNs and upper and lower bounds for multi-layer GCNs. Our simulated results suggest that the true maximum number of linear regions is likely closer to our estimated lower bound. These findings indicate that multi-layer GCNs have exponentially greater expressivity than one-layer GCNs per parameter, implying that deeper GCNs are more expressive than their shallow counterparts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis., Methods: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs)., Results: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002., Conclusion: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway., (© 2023. Huazhong University of Science and Technology.)

Background: The central biological clock governs numerous facets of mammalian physiology, including sleep, metabolism, and immune system regulation. Understanding gene regulatory relationships is crucial for unravelling the mechanisms that underlie various cellular biological processes. While it is possible to infer circadian gene regulatory relationships from time-series gene expression data, relying solely on correlation-based inference may not provide sufficient information about causation. Moreover, gene expression data often have high dimensions but a limited number of observations, posing challenges in their analysis., Methods: In this paper, we introduce a new hybrid framework, referred to as Circadian Gene Regulatory Framework (CGRF), to infer circadian gene regulatory relationships from gene expression data of rats. The framework addresses the challenges of high-dimensional data by combining the fuzzy C-means clustering algorithm with dynamic time warping distance. Through this approach, we efficiently identify the clusters of genes related to the target gene. To determine the significance of genes within a specific cluster, we employ the Wilcoxon signed-rank test. Subsequently, we use a dynamic vector autoregressive method to analyze the selected significant gene expression profiles and reveal directed causal regulatory relationships based on partial correlation., Conclusion: The proposed CGRF framework offers a comprehensive and efficient solution for understanding circadian gene regulation. Circadian gene regulatory relationships are inferred from the gene expression data of rats based on the Aanat target gene. The results show that genes Pde10a, Atp7b, Prok2, Per1, Rhobtb3 and Dclk1 stand out, which have been known to be essential for the regulation of circadian activity. The potential relationships between genes Tspan15, Eprs, Eml5 and Fsbp with a circadian rhythm need further experimental research., (© 2023. The Author(s).)

Objective: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture., Methods: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T 2 fracture, 1 case of T 3 fracture, 3 cases of T 4 fracture, 3 cases of T 5 fracture, and 7 cases of T 6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T 1 fracture, 5 cases of T 4 fracture, 2 cases of T 5 fracture and 9 cases of T 6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups., Results: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group( P <0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%( t =100.869, P <0.001; t =25.456, P <0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%( t =121.816, P <0.001; t =23.691, P <0.001). There was no significant difference in VAS and ODI between the two groups after operation ( t =-3.917, P =0.476; t =-0.922, P =0.364)., Conclusion: Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.

Background: The introduction of endovascular repair provides an alternative to traditional open repair of thoracoabdominal aortic aneurysms (TAAA). Its utility is not well defined, however. Using a national database, we studied the treatment patterns and outcomes of TAAA to gain insight into its contemporary surgical practice in the United States., Methods: Records of TAAA patients who received endovascular and open repair were retrieved from the 2002 to 2018 National Inpatient Sample database. Each cohort was stratified into 4 age groups: ≤50, 51 to 60, 61 to 70, and >70 years. Patient characteristics and in-hospital outcomes were compared between the 2 repair modalities. Temporal trends were investigated., Results: Endovascular repair use increased steadily, whereas open repair volume remained stable until 2012, before declining by 50% by 2018. This appears to be associated with a declining number of open repairs in patients age >60 years. Patients who underwent endovascular repair were older and had a higher Charlson Comorbidity Index (mean, 2.8 ± 1.7 vs 2.5 ± 1.5; P  < .001) but lower in-hospital mortality (mean, 8.9% vs 17.1%; P  < .001), shorter length of stay (mean, 10.1 ± 12.2 days vs 17.1 ± 17.4 days; P  < .001), and fewer postoperative complications. A difference in mortality between open and endovascular repair was observed for patients age >60 years but not for patients age ≤60 years., Conclusions: There has been a shift in the treatment of TAAA in the United States from open repair-dominant to endovascular repair-dominant. It has increased surgical access for older and more comorbid patients and has led to a decline in the use of open repair while lowering in-hospital mortality., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Objective: Compared thyroid volumes measured by 2-D and 3-D US with those of resected specimens and proposed new models to improve measurement accuracy., Methods: This study included 80 patients who underwent total thyroidectomy. One 2D&#95;model and one 3D&#95;model were developed using piecewise linear regression analysis. The accuracy of these models was compared using an ellipsoid model (2-D&#95;US value × 0.5), 3-D&#95;US value, and Ying's model [1.76 + (2-D&#95;US value × 0.38)]., Results: The new 2D&#95;model was: V=2.66 + (0.71 * X1) - (1.51 * X2). In this model, if 2-D&#95;US value <= 228.39, X1 = 2-D&#95;US value and X2 = 0; otherwise, X1 = 2-D&#95;US value and X2 = 2-D&#95;US value - 228.39. The 3D&#95;model was: V= 2.90 + (1.08 * X1) + (2.43 * X2). In this model, if 3-D&#95;US value <= 102.06, X1 = 3-D&#95;US value and X2 = 0; otherwise, X1 = 3-D&#95;US value and X2 = 3-D&#95;US value - 102.06. The accuracy of the new models was higher than that of the 3-D&#95;US value, the ellipsoid model, and Ying's model (P<0.05)., Conclusion: The models established are more accurate than the traditional ones and can accurately measure thyroid volume., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this work, we have proposed a Continuous Constant Potential Model (CCPM) based on grand canonical density functional theory for describing the electrocatalytic thermodynamics on single atom electrocatalysts dispersed on graphene support. The linearly potential-dependent capacitance is introduced to account for the net charge variation of the electrode surface and to evaluate the free energetics. We have chosen the CO2 electro-reduction reaction on single-copper atom catalysts, dispersed by nitrogen-doped graphene [CuNX@Gra (X = 2, 4)], as an example to show how our model can predict the potential-dependent free energetics. We have demonstrated that the net charges of both catalyst models are quadratically correlated with the applied potentials and, thus, the quantum capacitance is linearly dependent on the applied potentials, which allows us to continuously quantify the potential effect on the free energetics during the carbon dioxide reduction reaction instead of confining it to a specific potential. On the CuN4@Gra model, it is suggested that CO2 adsorption, coupled with an electron transfer, is a potential determining step that is energetically unfavorable even under high overpotentials. Interestingly, the hydrogen adsorption on CuN4@Gra is extremely easy to occur at both the Cu and N sites, which probably results in the reconstruction of the CuN4@Gra catalyst, as reported by many experimental observations. On CuN2@Gra, the CO2RR is found to exhibit a higher activity at the adjacent C site, and the potential determining step is shifted to the *CO formation step at a wide potential range. In general, CCPM provides a simple method for studying the free energetics for the electrocatalytic reactions under constant potential., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Aims: This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD)., Methods: The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions., Results: A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF-gene interaction and TF-miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD., Conclusion: The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Author(s) et al.)

Background: Salivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton-remodeling-related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial-mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated., Methods: An analysis of single-cell RNA sequencing (scRNA-seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues., Results: Our analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra-lesional heterogeneity. Cytoskeleton-remodeling-related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA., Conclusion: Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism., Methods: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines., Results: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis., Conclusion: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: MIKC type MADS-box transcription factors are one of the largest gene families and play a pivotal role in flowering time and flower development. Chimonanthus salicifolius belongs to the family Calycanthaceae and has a unique flowering time and flowering morphology compared to other Chimonanthus species, but the research on MIKC type MADS-box gene family of C. salicifolius has not been reported., Objective: Identification, comprehensive bioinformatic analysis, the expression pattern of MIKC-type MADS-box gene family from different tissues of C. salicifolius., Methods: Genome-wide investigation and expression pattern under different tissues of the MIKC-type MADS-box gene family in C. salicifolius, and their phylogenetic relationships, evolutionary characteristics, gene structure, motif distribution, promoter cis-acting element were performed., Results: A total of 29 MIKC-type MADS-box genes were identified from the whole genome sequencing. Interspecies synteny analysis revealed more significant collinearity between C. salicifolius and the magnoliids species compared to eudicots and monocots. MIKC-type MADS-box genes from the same subfamily share similar distribution patterns, gene structure, and expression patterns. Compared with Arabidopsis thaliana, Nymphaea colorata, and Chimonanthus praecox, the FLC genes were absent in C. salicifolius, while the AGL6 subfamily was expanded in C. salicifolius. The selectively expanded promoter (AGL6) and lack of repressor (FLC) genes may explain the earlier flowering in C. salicifolius. The loss of the AP3 homologous gene in C. salicifolius is probably the primary cause of the morphological distinction between C. salicifolius and C. praecox. The csAGL6a gene is specifically expressed in the flowering process and indicates the potential function of promoting flowering., Conclusion: This study offers a genome-wide identification and expression profiling of the MIKC-types MADS-box genes in the C. salicifolius, and establishes the foundation for screening flowering development genes and understanding the potential function of the MIKC-types MADS-box genes in the C. salicifolius., (© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Genomic structural variations (SVs) are widespread in plant and animal genomes and play important roles in phenotypic novelty and species adaptation. Frequent whole genome duplications followed by (re)diploidizations have resulted in high diversity of genome architecture among extant species. In this study, we identified abundant genomic SVs in the Panax genus that are hypothesized to have occurred through during the repeated polyploidizations/(re)diploidizations. Our genome-wide comparisons demonstrated that although these polyploidization-derived SVs have evolved at distinct evolutionary stages, a large number of SV-intersecting genes showed enrichment in functionally important pathways related to secondary metabolites, photosynthesis and basic cellular activities. In line with these observations, our metabolic analyses of these Panax species revealed high diversity of primary and secondary metabolites both at the tissue and interspecific levels. In particular, genomic SVs identified at ginsenoside biosynthesis genes, including copy number variation and large fragment deletion, appear to have played important roles in the evolution and diversification of ginsenosides. A further herbivore deterrence experiment demonstrated that, as major triterpenoidal saponins found exclusively in Panax, ginsenosides provide protection against insect herbivores. Our study provides new insights on how polyploidization-derived SVs have contributed to phenotypic novelty and plant adaptation., (© 2023 John Wiley & Sons Ltd.)

Background: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine., Methods: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes., Results: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine., Conclusions: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAF V600E gene encodes a protein-dependent kinase (PDK), which is a key component of the mitogen-activated protein kinase pathway and essential for controlling cell proliferation, differentiation, and death. The BRAF V600E mutation causes PDK to be activated improperly and continuously, resulting in abnormal proliferation and differentiation in PTC. Based on elastography ultrasound (US) radiomic features, this study seeks to create and validate six distinct machine learning algorithms to predict BRAF V6OOE mutation in PTC patients prior to surgery. This study employed routine US strain elastography image data from 138 PTC patients. The patients were separated into two groups: those who did not have the BRAF V600E mutation (n = 75) and those who did have the mutation (n = 63). The patients were randomly assigned to one of two data sets: training (70%), or validation (30%). From strain elastography US images, a total of 479 radiomic features were retrieved. Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified tenfold cross-validation were used to decrease the features. Based on selected radiomic features, six machine learning algorithms including support vector machine with the linear kernel (SVM&#95;L), support vector machine with radial basis function kernel (SVM&#95;RBF), logistic regression (LR), Naïve Bayes (NB), K-nearest neighbors (KNN), and linear discriminant analysis (LDA) were compared to predict the possibility of BRAF V600E . The accuracy (ACC), the area under the curve (AUC), sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), decision curve analysis (DCA), and calibration curves of the machine learning algorithms were used to evaluate their performance. ① The machine learning algorithms' diagnostic performance depended on 27 radiomic features. ② AUCs for NB, KNN, LDA, LR, SVM&#95;L, and SVM&#95;RBF were 0.80 (95% confidence interval [CI]: 0.65-0.91), 0.87 (95% CI 0.73-0.95), 0.91(95% CI 0.79-0.98), 0.92 (95% CI 0.80-0.98), 0.93 (95% CI 0.80-0.98), and 0.98 (95% CI 0.88-1.00), respectively. ③ There was a significant difference in echogenicity,vertical and horizontal diameter ratios, and elasticity between PTC patients with BRAF V600E and PTC patients without BRAF V600E . Machine learning algorithms based on US elastography radiomic features are capable of predicting the likelihood of BRAF V600E in PTC patients, which can assist physicians in identifying the risk of BRAF V600E in PTC patients. Among the six machine learning algorithms, the support vector machine with radial basis function (SVM&#95;RBF) achieved the best ACC (0.93), AUC (0.98), SEN (0.95), SPEC (0.90), PPV (0.91), and NPV (0.95)., (© 2023. Springer Nature Limited.)

The effect of plugging the puncture channel with a mixture of hemocoagulase injection on the complications of CT-guided percutaneous transthoracic need biopsy (PTNB) was discussed. The medical records of PTNB were retrospectively studied from June 2017 to May 2022. In the study, the puncture channel of 626 patients were blocked, while remain 681 patients' were not. The Mantel Haenszel method performed layered analysis and evaluated the correlation of adjusted confounding factors. The Odds Ratio and its 95% confidence interval were calculated using the Woof method. The incidence of high-level pulmonary hemorrhage was significantly reduced in patients with lesions ≤ 2 cm and different needle lengths. Patients with different pleural-needle tip angle and perineedle emphysema were blocked, and the incidence of pneumothorax and thoracic implants was significantly reduced. Through puncture channel plugging, the incidence of pulmonary hemorrhage, pneumothorax and thoracic catheterization of PTNB under CT guidance was reduced., (© 2023. The Author(s).)

Many people suffer from hair loss and abnormal skin pigmentation, highlighting the need for simple assays to support drug discovery research. Current assays have various limitations, such as being in vitro only, not sensitive enough, or unquantifiable. We took advantage of the bilateral symmetry and large size of mouse whisker follicles to develop a novel in vivo assay called "whisker follicle microinjection assay". In this assay, we plucked mouse whiskers and then injected molecules directly into one side of the whisker follicles using microneedles that were a similar size to the whiskers, and we injected solvent on the other side as a control. Once the whiskers grew out again, we quantitatively measured their length and color intensity to evaluate the effects of the molecules on hair growth and coloring. Several chemicals and proteins were used to test this assay. The chemicals minoxidil and ruxolitinib, as well as the protein RSPO1, promoted hair growth. The effect of the clinical drug minoxidil could be detected at a concentration as low as 0.001%. The chemical deoxyarbutin inhibited melanin production. The protein Nbl1 was identified as a novel hair-growth inhibitor. In conclusion, we successfully established a sensitive and quantitative in vivo assay to evaluate the effects of chemicals and proteins on hair growth and coloring and identified a novel regulator by using this assay. This whisker follicle microinjection assay will be useful when investigating protein functions and when developing drugs to treat hair loss and abnormal skin pigmentation.

This study aimed to investigate the relationship between depression and outcome of percutaneous endoscopic lumbar discectomy (PELD) in patients with lumbar disc herniation. We examined 268 patients who underwent PELD for lumbar disc herniation and were followed for five years. Patients were grouped according to mood: normal mood (159 patients) and continuous depression (109 patients). Depressive symptoms were assessed using the 21-item Beck Depression Inventory. Back and leg pain were assessed using the visual analogue scale. Subjective disability was measured using the Oswestry Disability Index. Neurological function and physical disability were assessed using the Japanese Orthopaedic Association score. Disc-height ratio and intervertebral instability were measured to assess lumbar stability. Clinical and radiological data were recorded before surgery and at the 3-month, 6-month, 1-year, 2-year, and 5-year follow-ups. Although the Japanese Orthopaedic Association, visual analogue scale, and Oswestry Disability Index scores did not significantly differ between groups before surgery, all three scores significantly differed between groups at all follow-up time points after PELD (p < 0.05). Measurements of disc-height ratio and intervertebral instability did not significantly differ between the groups before surgery nor at any point after surgery (P > 0.05). Patients with continuous depression exhibited less improvement in symptom severity and disability score after PELD at all time points in the five years after surgery. Depression had little effect on lumbar vertebral stability after PELD. Interventions to detect and treat depression should be performed before and after surgery.

Objective: This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes., Research Design and Methods: A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan-Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients., Results: The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients., Conclusions: The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis., (© 2023. The Author(s).)

The design of active and low-cost electrocatalyst for hydrogen evolution reaction (HER) is the key to achieving a clean hydrogen energy infrastructure. The most successful design principle of hydrogen electrocatalyst is the activity volcano plot, which is based on Sabatier principle and has been used to understand the exceptional activity of noble metal and design of metal alloy catalysts. However, this application of volcano plot in designing single-atom electrocatalysts (SAEs) on nitrogen doped graphene (TM/N 4 C catalysts) for HER has been less successful due to the nonmetallic nature of the single metal atom site. Herein, by performing ab initio molecular dynamics simulations and free energy calculations on a series of SAEs systems (TM/N 4 C with TM = 3d, 4d, or 5d metals), we find that the strong charge-dipole interaction between the negatively charged *H intermediate and the interfacial H 2 O molecules could alter the transition path of the acidic Volmer reaction and dramatically raise its kinetic barrier, despite its favorable adsorption free energy. Such kinetic hindrance is also experimentally confirmed by electrochemical measurements. By combining the hydrogen adsorption free energy and the physics of competing interfacial interactions, we propose a unifying design principle for engineering the SAEs used for hydrogen energy conversion, which incorporates both thermodynamic and kinetic considerations and allows going beyond the activity volcano model.

Tungsten and molybdenum carbides have shown great potential in catalysis and superconductivity. However, the synthesis of ultrathin W/Mo carbides with a controlled dimension and unique structure is still difficult. Here, inspired by the host-guest assembly strategy with single-walled carbon nanotubes (SWCNTs) as a transparent template, we reported the synthesis of ultrathin (0.8-2.0 nm) W 2 C and Mo 2 C nanowires confined in SWCNTs deriving from the encapsulated W/Mo polyoxometalate clusters. The atom-resolved electron microscope combined with spectroscopy and theoretical calculations revealed that the strong interaction between the highly carbophilic W/Mo and SWCNT resulted in the anisotropic growth of carbide nanowires along a specific crystal direction, accompanied by lattice strain and electron donation to the SWCNTs. The SWCNT template endowed carbides with resistance to H 2 O corrosion. Different from normal modification on the outer surface of SWCNTs, such M 2 C@SWCNTs (M = W, Mo) provided a delocalized and electron-enriched SWCNT surface to uniformly construct the negatively charged Pd catalyst, which was demonstrated to inhibit the formation of active PdH x hydride and thus achieve highly selective semihydrogenation of a series of alkynes. This work could provide a nondestructive way to design the electron-delocalized SWCNT surface and expand the methodology in synthesizing unusual 1D ultrathin carbophilic-metal nanowires (e.g., TaC, NbC, β-W) with precise control of the anisotropy in SWCNT arrays.

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P< 0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M (IQR), Z= 3.023, P< 0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t =6.524, P< 0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

Introduction: Compared with fixed treatments, clear aligners (CAs) have the advantages of comfort, esthetics, and hygiene, and are popular among patients and orthodontists. However, CAs exhibit control deficiencies in extraction patients because of insufficient root control and retention effects. These deficiencies can magnify biomechanical differences in bimaxillary dentition, further causing different orthodontic requirements between maxillary and mandibular dentition. This study aimed to elaborate on the biomechanical characteristics of bimaxillary dentition in extraction space closure and provided feasible biomechanical compensation strategies for use in clinical practice., Methods: We constructed a 3-dimensional (3D) bimaxillary model based on patient data. Several 3D modeling-related software was used to generate a standard first premolar extraction model, CAs, and attachments. Subsequently, finite element analysis was performed to demonstrate the biomechanical effects., Results: The maxillary and mandibular dentition showed a roller coaster effect during space closure. Compared with the maxillary dentition, the mandibular posterior teeth exhibited stronger relative anchorage causing greater anterior teeth retraction. The tipping and vertical movements of the anterior teeth were related to tooth length. The longer the anterior tooth, the less tipping and greater vertical displacement occurred. Generally, when having the same retraction distance, the mandibular dentition exhibited greater retroclination and fewer extrusions. Both mechanical and retention compensations should be considered to prevent these unwanted tipping movements. Adding specific attachments to bimaxillary dentitions compensated for the retention and root control deficiencies of CAs., Conclusions: When applying CAs to extraction patients, different biomechanical effects can present in the bimaxillary dentition because of specific dentition morphologies. To effectively treat these patients, mechanical compensation through overcorrection of the target position should be designed on the basis of bimaxillary control deficiencies, and retention compensation by adding specific attachments should also be considered according to the overcorrections., (Copyright © 2023. Published by Elsevier Inc.)

Background: This study explored the feasibility of using EEG gamma-band (30-49 Hz) power as an index of cue-elicited craving in METH-dependent individuals., Methods: Twenty-nine participants dependent on methamphetamine (METH) and 30 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment., Results: Individuals with METH dependence showed significantly stronger self-reported craving and higher gamma power in a VR environment than healthy individuals. In the METH group, the VR environment elicited a significant increase in gamma power compared with the resting state. The METH group then received a VR counterconditioning procedure (VRCP), which was deemed useful in suppressing cue-induced reactivity. After VRCP, participants showed significantly lower self-reported craving scores and gamma power when exposed to drug-related cues than the first time., Conclusions: These findings suggest that the EEG gamma-band power may be a marker of cue-induced reactivity in patients with METH dependence., (© 2023. The Author(s).)