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ABSTRACTEpithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.

BackgroundEvidence about the association between air pollution and carotid intima-media thickness (CIMT) is inconsistent, and limited studies have explored the relationship between gaseous pollutants and CIMT. Additionally, personal activity patterns and infiltrated ambient pollution are not comprehensively considered to estimate individual exposure to air pollutants. ObjectiveTo investigate the relationship between long-term time-weighted individual exposure to ambient pollutants [fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO)] and the progression of CIMT. MethodsThis study was performed among 554 participants in the Beijing Health Management Cohort who were free of atherosclerotic lesions on carotid artery at baseline. Daily concentrations of pollutants were predicted at both residential and work addresses based on land-use regression model. With additional consideration of personal indoor and outdoor activity patterns at both addresses and exposure to ambient pollutants from traffic transportation, individual time-weighted concentration was calculated. Indoor exposure was estimated by infiltrated ambient pollutants (based on infiltration factors and land-use regression model). Personal activity patterns included type, time, location, and frequency. Exposure to ambient pollutants from different traffic transportations was estimated by the average outdoor pollutant concentrations at both residential and work addresses combined within filtration factors and time spent on commuting. Multiple linear regression was conducted to assess the association of time-weighted individual pollutant exposure and the central position of CIMT progression. Quantile regression was applied to explore the relationship between time-weighted individual pollutant exposure and the progression of CIMT on different percentiles. ResultsThe median value of CIMT progression was 369.49 μm·year−1. PM2.5, PM10, SO2, and O3 were associated with CIMT progression in the multiple linear regression model. The largest effect sizes of PM2.5, PM10, and SO2 were obtained for one-year exposure (regression coefficient: 66.910, 64.077, and 191.070, respectively), and two-year exposure for O3 (regression coefficient: 62.197). The results of quantile regression demonstrated different effect sizes for pollutants among different percentiles on CIMT progression. Significant associations between CIMT progression and PM2.5 from P30 to P50, CO from P10 to P40, and PM10 from P30 to P60 were observed. Two-year and three-year exposures to NO2 (P10, P20 and P40) were also associated with CIMT progression. The association between SO2 and the progression of CIMT was proved on all percentiles, and larger effect sizes of one-year and two-year exposures to SO2 (except P90) were demonstrated with increasing percentiles. The upward trend for the coefficients was clearly presented from P50 to P80. Specifically, the coefficient of two-year exposure to SO2 ranged from 136.583 (P50) to 277.330 (P80). No statistically significant association was observed between O3 and CIMT progression on any percentile (P>0.05), and the results were inconsistent with those of the multiple linear regression. ConclusionIndividual time-weighted exposures to PM2.5, PM10, SO2, NO2, and CO have the potential to promote the progression of CIMT, and the adverse effect of ambient pollution on atherosclerotic lesion is identified.

Abstract Protein phosphatase 2A (PP2A) is usually a heterotrimeric enzyme, consisting of a catalytic subunit (C) and a scaffolding subunit (A) associated with a third, variable regulatory subunit (B). Fungi usually carry a single gene for A and C subunits, and three genes for the B subunit. In addition, fungi contain a conserved atypical C subunit named Ppg1, which is essential to the pathogenicity of the rice blast fungus Magnaporthe oryzae. However, it remains largely unknown how the B subunit combinatorically assembles with the A and C subunits or Ppg1 to regulate fungal growth, development and pathogenicity. Here we report and functionally characterize one regulatory subunit of PP2A, named MoB56, in M. oryzae. We generated a MoB56 deletion mutant Δmob56, which was severely defective in vegetative growth, conidiation and septum formation, and had lost pathogenicity. The defects of Δmob56 could be rescued by introducing MoB56 fused with GFP (MoB56-GFP) at its C terminus. Fluorescence microscopic observations revealed that the MoB56-GFP signals were widely distributed in the cytoplasm and formed a dot-like structure at the center of the septum in conidia, appressoria and infection hyphae, supporting its function in septation. Further, we performed co-immunoprecipitation and pull-down assays, indicating that MoB56 forms a protein complex with the A subunit and Ppg1 in mycelial cells. The yeast two-hybrid assay showed that MoB56 could interact with the A subunit of PP2A but not with Ppg1, while Ppg1 could interact with the A subunit, suggesting that the A subunit ties MoB56 with Ppg1 for the protein complex formation. In addition, we revealed that MoB56 has multiple isoforms, which are likely originated from alternative splicing and sumoylation. This is the first report revealing that the regulatory subunit B56 is associated with the PP2A-like phosphatase Ppg1 in fungi. Importantly, this study showed that B56, like Ppg1, is essential to the pathogenicity of M. oryzae, offering a potential new lead to control this devastating fungal pathogen by targeting specific PP2A-like phosphatase. Together, this study provides important information for understanding how the regulatory subunit B56 of PP2A regulates fungal pathogenicity and for the control of rice blast disease.

Abstract Backgroud With the reform of medical system in China, Beijing municipal hospitals explored a new pharmaceutical care model and set up medication therapy management services (MTMs) in ambulatory care since 2019. We were one of the first hospitals to set up this service in China. At the present, there were relatively few reports about the effect of MTMs in China. In this study, we summarized the implementation of MTMs in our hospital, explore the feasibility of pharmacist-led MTMs in ambulatory care and the impact of MTMs on patients’ medical costs. Methods A retrospective study was conducted in a university-affiliated, tertiary comprehensive hospital in Beijing, China. The patients who received at least one MTMs and with complete medical records and pharmaceutical documents from May 2019 to February 2020 were included. Pharmacists provided pharmaceutical care for patients according to the MTMs standards issued by the American Pharmacists Association, identified the numbers and classification of the patients’ perceived medication-related demands, identified medication-related problems (MRPs), and developed the medication-related action plans (MAPs). All MRPs found by pharmacists, pharmaceutical interventions, and resolving recommendations were documented, and calculate the cost of treatment drugs that patients can reduce. Results A total of 112 patients received MTMs in ambulatory care, among them 81 cases with the completed record were included in this study. 67.9% of patients had five or more diseases, 83% of them co-took over 5 drugs. While performing MTMs, 128 patients’ perceived medication-related demands were recorded in all, monitoring and judgment of adverse drug reaction (ADR) (17.19%) was the most common demand. 181 MRPs were found, with an average of 2.55 MPRs per patient. Nonadherence (38%), excessive drug treatment (20%), and adverse drug events (17.12%) were the top three MRPs. Pharmaceutical care (29.77%), adjustment of drug treatment plan (29.10%) and referral to the clinical department (23.41%) were the top three MAPs. Whereby the MTMs provided by pharmacists, the cost-saving of each patient was about $ 43.2 monthly. Conclusion By participating in the MTMs of outpatients, the pharmacists could identify more MRPs and develop personalized MAPs timely for patients, thereby promoting rational drug use and reducing medical expenses.

Tailoring both the core size and shell thickness of core-shell bimetallic nanocatalysts to the dedicated geometrical and electronic properties are vital for catalytic performance optimization. Here the authors demonstrate such conjugated dual particle size effects on Au@Pd catalyzed benzyl alcohol oxidation.

Debris flow early warning is an effective method to prevent major disasters, so a multi-index fusion debris flow early warning model based on spatial interpolation and a support vector machine is designed. Aiming at the discrete rainfall data in the study area, the collaborative Kriging spatial interpolation method based on Kriging spatial interpolation is adopted to process the rainfall data into multi-index fused surface data. The rainfall data after spatial interpolation are used as the input sample data of the support vector machine early warning model, and the optimal parameters of the support vector machine are calculated by the sea squirt algorithm, and then the debris flow early warning results are output. After experimental analysis, the model can obtain rainfall surface data. After calculation by the model, the accuracy of the early warning probability of debris flow is improved, and the early warning result is consistent with the actual result of debris flow.

As the demand for alternative protein sources and nutritional improvement in baked goods grows, integrating legume-based ingredients, such as fava beans, into wheat flour presents an innovative alternative. This study investigates the potential of hyperspectral imaging (HSI) to predict the protein content (short-wave infrared (SWIR) range)) of fava bean-fortified bread and classify them based on their color characteristics (visible–near-infrared (Vis-NIR) range). Different multivariate analysis tools, such as principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and partial least square regression (PLSR), were utilized to assess the protein distribution and color quality parameters of bread samples. The result of the PLS-DA in the SWIR range yielded a classification accuracy of ˃99%, successfully classifying the samples based on their protein contents (low protein and high protein). The PLSR model showed an RMSEC of 0.086% and an RMSECV of 0.094%. Also, the external validation resulted in an RMSEP of 0.064%. The PLSR model possessed the capability to efficiently predict the protein content of the bread samples. The results suggest that HSI can be successfully used to classify bread samples based on their protein content and for the prediction of protein composition. Hyperspectral imaging can therefore be reliably implemented for the quality monitoring of baked goods in commercial bakeries.

Abstract Few studies have explored the effects of fine particulate matter (PM2.5) and its constituents on the progression of cerebral blood flow velocity (BFV) and the potential modifying role of greenness. In this study, we investigated the association of PM2.5 and its constituents, including sulfate (SO42−), nitrate (NO3−), ammonium (NH4+), organic matter (OM), and black carbon (BC), with the progression of BFV in the middle cerebral artery. Participants from the Beijing Health Management Cohort who underwent at least two transcranial Doppler sonography examinations during 2015–2020 were recruited. BFV change and BFV change rate were used to define the progression of cerebral BFV. Linear mixed effects models were employed to analyze the data, and the weighted quantile sum regression assessed the contribution of PM2.5 constituents. Additionally, greenness was examined as a modifier. Among the examined constituents, OM exhibited the strongest association with BFV progression. An interquartile range increase in PM2.5 and OM exposure concentrations was associated with a decrease of −16.519 cm/s (95% CI: −17.837, −15.201) and −15.403 cm/s (95% CI: −16.681, −14.126) in BFV change, and −10.369 cm/s/year (95% CI: −11.387, −9.352) and −9.615 cm/s/year (95% CI: −10.599, −8.632) in BFV change rate, respectively. Furthermore, stronger associations between PM2.5 and BFV progression were observed in individuals working in areas with lower greenness, those aged under 45 years, and females. In conclusion, reducing PM2.5 levels in the air, particularly the OM constituent, and enhancing greenness could potentially contribute to the protection of cerebrovascular health.

Background We aimed to examine separate and joint associations of remnant cholesterol (RC) accumulation and variability with the risk of carotid atherosclerosis (CAS) in the general population. Methods and Results A total of 6213 participants who underwent 3 sequential health examinations during 2010 to 2015 were enrolled and were followed up until December 31, 2021. Cumulative RC (cumRC) and RC variability among the 3 visits were the exposure of interest in our study. Adjusted Cox models were performed to calculate the hazard ratio (HR) and 95% CI. C‐statistics, integrated discrimination improvement, and the net reclassification index were used to estimate the incremental predictive ability. During a median follow‐up of 4.00 years, 2613 participants developed CAS. Higher cumRC (HR, 1.33 [95% CI, 1.17–1.52]) and greater RC variability (HR, 1.22 [95% CI, 1.08–1.39]) were significantly associated with elevated risk of CAS, independent of traditional cardiovascular risk factors and low‐density lipoprotein cholesterol. Participants were divided into 4 groups according to the median of cumRC and RC variability to assess their joint associations. Compared with “low cumRC and low variability,” “high cumRC and high variability” had the highest risk of CAS, followed by “high cumRC and low variability” and “low cumRC and high variability.” Finally, joint assessment of RC accumulation and variability had the significantly highest incremental effect on the predictive value of CAS versus single‐time‐point measures of RC. Conclusions Excessive cumRC levels and greater RC variability were each independently associated with higher incidence of CAS, and their coexistence could further yield significantly higher risks.

Large-scale application of reclaimed asphalt and modifiers in asphalt admixtures make a claim for the component regulation mechanism of asphalt thus to improve the mechanical properties of asphalt admixtures. In this study, the effects of component characteristics on the micromechanical properties of three common asphalts (AAA-1, AAM-1 and AAK-1) collected in the Strategic Highway Research Program's Materials Reference Library were studied by using molecular dynamics simulation methods. The physical and mechanical properties of these asphalts were simulated, including density, glassy transition temperature (Tg), flow temperature (Tf), bulk modulus, shear modulus and Young's modulus. In addition, an aggregate-asphalt-aggregate model was constructed to simulate a confined shear case to explore the contribution of different components to the mechanical properties of the asphalt mixture. The results show that the densities of AAA-1, AAK-1 and AAM-1 asphalt models are 0.991 ± 0.005 g/cm3, 1.00 ± 0.005 g/cm3 and 0.968 ± 0.004 g/cm3, which verify the rationality of the models. The Tg of AAA-1, AAK-1 and AAM-1 asphalt models are 253.70 K, 268.74 K and 257.55 K, respectively, which are consistent with the experimental results of the Differential Scanning Calorimeter. The Tf of AAA-1, AAK-1 and AAM-1 asphalt models are 361.26 K, 374.48 K and 374.95 K, respectively. The diffusion of resin and aromatic are sensitive to temperature from mean squared displacement (MSD) analysis. The bulk modulus, shear modulus and Young’s modulus of the AAM-1 asphalt model are 3.254 GPa, 0.757 GPa and 2.109 GPa, which are the highest among these three models due to its highest relative molecular mass and resin content. The confined shear simulation on the aggregate-asphalt-aggregate model shows that the shear strength between aggregate and AAM-1 asphalt is the strongest, followed by the case of AAA-1 and AAK-1, in keeping with the sequence of the shear modulus of three asphalts. Asphaltene has the largest MSD and contributes greatly to the adhesion between the asphalt and aggregate interface during the confined shear. These computed parameters could be the basis for the design of high-modulus asphalt admixture applicated in different environments.

Network embedding aims to represent nodes in unstructured network with low-dimensional,real-valued vectors,so that node embedding can retain the structural and attribute features of the original network as much as possible.However,current research mainly focuses on embedding the network structure.There are few researches considering relationship attributes and node attributes with rich semantics in heterogeneous information networks,which mayresult in semetic loss of node embedding and affect the prediction effect of downstream applications.To solve this problem,this paper designs a method of attributed heteroge-neous network embedding with multiple features(MFAHNE).This method integrates the relationship attributes,node attributes and structural semantics in the network into the final node embedding through the steps of sampling sequence,embedding with structural feature,embedding with attribute feature and merging features.Experiment result shows that this method can take into account the structural feature and attribute features,realizes the mutual supplement of two kinds of feature information,and is better than the traditional network embedding methods.

As a new computing paradigm,edge computing provides computing and storage services at the edge of the network compared to traditional cloud computing model.It has the characteristics of high reliability and low latency.However,there are still some problems in privacy protection and data processing.As a distributed machine learning model,federated learning can well solve the problems of inconsistent data distribution and data privacy in edge computing scenarios,but it still faces challenges in equipment heterogeneity,data heterogeneity and communication,such as model offset,the convergence effect is poor,and the calculation results of some devices are lost.In order to solve the above problems,a federated learning optimization algorithm with dynamic weights(FedDw) is proposed,which focuses on the service quality of the equipment,reduces the heterogeneous impact caused by the participation of some equipments due to inconsistent training speed,and determines the proportion in the final mo-del aggregation according to the service quality,so as to ensure that the aggregation results are more robust in complex real situations.Through experiments,the two excellent federated learning algorithms,FedProx and Scaffold,are compared on the real data sets of 10 regional weather stations.The results show that the FedDw algorithm has better comprehensive performance.

Background: The repair of alar defects is challenging in clinics. Although skin grafts and nasolabial flaps are reliable, they can cause secondary post-surgical deformities. Methods: In this report, we describe an alar spiral advancement flap with a subcutaneous pedicle combined with postoperative nasal stent therapy for the repair of alar defects. Results: All cases showed slight asymmetry immediately after surgery, but at a median follow-up of 24 months, no cases of dissatisfaction with the nose shape or abnormal respiratory function were found. Almost all incision scars subsided within 12 months. In addition, all flaps that were dissected and rotated during the surgeries healed, and no signs of necrosis or development of vascular compromise were observed. Conclusion: Our preliminary experience suggests that the alar spiral flap followed by nasal stent therapy provides stable recovery of appearance and function for alar defects during follow-ups and shows promise for future therapies.

Abstract Objective To compare and analyze the pass rate and screening strategy of hearing rescreening for newborns with high risk factors. Methods Retrospective chart review of high‐risk newborns who failed their initial newborn hearing screen and subsequently underwent secondary hearing tests from June 2011 to June 2018 in Guangzhou Women and Children's Medical Center were performed. Results Eight hundred and sixty‐eight newborns with high risk factors were included in the study. The 57‐70 days (83.5%) and 71‐84 days (83.4%) group had the highest pass rate compared with 42‐56 days (75.8%) and < 42 days (68.3%) group. As for different screening strategies, the pass rate of OAE(otoacoustic emissions), AABR (auto auditory brainstem response) and OAE + AABR was the highest in 57–70 days group and 71‐84 days group, respectively. The OAE + AABR had the lowest pass rate compared to the other two modalities. When the pass rate was compared as different risk factors, the 57–70 days and 71–84 days group also had the highest pass rate compared with 42–56 days and < 42 days group and the pass rate had no significant differences among various risk factors group. Conclusion Our results showed that all the pass rate of OAE, AABR and OAE + AABR was the highest in 57–70 days group and 71–84 days group with significant difference, suggesting that the delayed screening time (>57 days) may increase the re‐screening pass rate and reduce anxiety of parents, which is of great significance for clinical work.

The trends in annual precipitation and wind induced by tropical cyclones (TCs) over Shanghai during the last 40 years are estimated. Results indicate that there is a significant increasing trend in the annual total precipitation induced by TCs, which is related to the significant positive trends in daily precipitation and annual torrential rain days. Meanwhile, a significant decreasing trend shows in maximum sustained wind, which seems to be related to the downward trend in the intensity of TCs when affecting Shanghai. The annual frequencies of affected TCs, TC translation speed and distance from Shanghai when affecting Shanghai have no obvious tendency. The different trends in precipitation and wind suggested that a more comprehensive metric for assessing TCs' influence on society is necessary.

Abstract Metabolic‐associated fatty liver disease (MAFLD) is a series of liver diseases based on liver steatosis and metabolic disorders. Steatosis, as the core factor in MAFLD diagnosis, and fibrosis, as the major determinant of adverse outcomes of MAFLD, need to be assessed simply and accurately. In this study, we explored the significance of mid‐upper arm circumference (MUAC) in evaluating liver steatosis and fibrosis in patients with MAFLD. We included 2397 cases with MAFLD from the 2017–2018 National Health and Nutrition Examination Surveys (NHANES) database. Liver steatosis and fibrosis were measured by vibration controlled transient elastography. Anthropometric parameters and demographic and serological data were obtained from the NHANES database. The association between MUAC and liver steatosis and fibrosis were evaluated by a multivariable linear regression model, a weighted generalized additive model, and smooth curve fitting using R. MUAC was positively associated with liver steatosis in every multivariate linear regression model (model 1: β = 3.3513; 95% confidence interval [CI], 2.7722–3.9304; model 2: β = 3.8492; 95% CI, 3.2441–4.4542; model 3: β = 2.4987; 95% CI, 1.8371–3.1604), and this positive association was consistent in both men and women and among different race groups (Mexican American, other Hispanic, non‐Hispanic White, Black, Asian, and other race). On the other hand, MUAC was positively associated with liver fibrosis in every multivariate linear regression model, and this positive association also was consistent in both men and women and among non‐Hispanic White and Black populations. Increased MUAC was positively associated with liver steatosis and fibrosis in patients with MAFLD. This was particularly true for MUAC ≥ 42.0 cm. MUAC might be a simple and convenient evaluation tool for MAFLD.

Plant fungal pathogens secrete numerous proteins into the apoplast at the plant–fungus contact sites to facilitate colonization. However, only a few secretory proteins were functionally characterized in Magnaporthe oryzae, the fungal pathogen causing rice blast disease worldwide. Asparagine-linked glycosylation 3 (Alg3) is an α-1,3-mannosyltransferase functioning in the N-glycan synthesis of N-glycosylated secretory proteins. Fungal pathogenicity and cell wall integrity are impaired in Δalg3 mutants, but the secreted proteins affected in Δalg3 mutants are largely unknown. In this study, we compared the secretomes of the wild-type strain and the Δalg3 mutant and identified 51 proteins that require Alg3 for proper secretion. These proteins were predicted to be involved in metabolic processes, interspecies interactions, cell wall organization, and response to chemicals. Nine proteins were selected for further validation. We found that these proteins were localized at the apoplastic region surrounding the fungal infection hyphae. Moreover, the N-glycosylation of these proteins was significantly changed in the Δalg3 mutant, leading to the decreased protein secretion and abnormal protein localization. Furthermore, we tested the biological functions of two genes, INV1 (encoding invertase 1, a secreted invertase) and AMCase (encoding acid mammalian chinitase, a secreted chitinase). The fungal virulence was significantly reduced, and the cell wall integrity was altered in the Δinv1 and Δamcase mutant strains. Moreover, the N-glycosylation was essential for the function and secretion of AMCase. Taken together, our study provides new insight into the role of N-glycosylated secretory proteins in fungal virulence and cell wall integrity.

Here the authors show that protein phase separation is a key mechanism in cellular receptor internalization via fast endophilin mediated endocytosis (FEME). Phase separation facilitates multivalent FEME-protein assembly in this clathrin-independent pathway.

Bin/Amphiphysin/Rvs (BAR) proteins are known as classical membrane curvature generators during endocytosis. Amphiphysin, a member of the N-BAR sub-family of proteins that contain a characteristic amphipathic sequence at the N-terminus of the BAR domain, is involved in clathrin-mediated endocytosis. Full-length amphiphysin contains a ~ 400 amino acid long disordered linker connecting the N-BAR domain and a C-terminal Src homology 3 (SH3) domain. We express and purify recombinant amphiphysin and its N-BAR domain along with an N-terminal glutathione-S-transferase (GST) tag. The GST tag allows extraction of the protein of interest using affinity chromatography and is removed in the subsequent protease treatment and ion-exchange chromatography steps. In the case of the N-BAR domain, cleavage of the GST tag was found to cause precipitation. This issue can be minimized by adding glycerol to the protein purification buffers. In the final step, size exclusion chromatography removes any potential oligomeric species. This protocol has also been successfully used to purify other N-BAR proteins, such as endophilin, Bin1, and their corresponding BAR domains.Graphical overview

Self-efficacy is a vital personal characteristic for student success. However, the challenge of cross-cultural comparisons remains as scalar invariance is hard to be satisfied. Also, it is unclear how to contextually understand student self-efficacy in light of cultural values in different countries. This study implements a novel alignment optimization method to rank the latent means of student self-efficacy of 308,849 students in 11,574 schools across 42 countries and economies that participated in the 2018 Program in International Student Assessment. We then used classification and regression trees to classified countries with differential latent means of student self-efficacy into groups according to Hofstede’s six cultural dimensions theory. The results of the alignment method recovered that Albania, Colombia, and Peru had students with the highest mean self-efficacy, while Slovak Republic, Moscow Region (RUS), and Lebanon had the lowest. Moreover, the CART analysis indicated a low student self-efficacy for countries presenting three features: (1) extremely high power distance; (2) restraint; and (3) collectivism. These findings theoretically highlighted the significance of cultural values in shaping student self-efficacy across countries and practically provided concrete suggestions to educators on which countries to emulate such that student self-efficacy could be promoted and informed educators in secondary education institutes on the international expansion of academic exchanges.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a global commonly occurring liver disease. However, its exact pathogenesis is not fully understood. The purpose of this study was to quantitatively evaluate the progression of steatosis and fibrosis by examining their distribution, morphology, and co-localization in NAFLD animal models.MethodsSix mouse NAFLD groups were established: (1) western diet (WD) group; (2) WD with fructose in drinking water (WDF) group; (3) WDF + carbon tetrachloride (CCl4) group, WDF plus intraperitoneal injection of CCl4; (4) high-fat diet (HFD) group, (5) HFD with fructose (HFDF) group; and (6) HFDF + CCl4 group, HFDF plus intraperitoneal injection of CCl4. Liver tissue specimens from NAFLD model mice were collected at different time points. All the tissues were serially sectioned for histological staining and second-harmonic generation (SHG)/two-photon excitation fluorescence imaging (TPEF) imaging. The progression of steatosis and fibrosis was analyzed using SHG/TPEF quantitative parameters with respect to the non-alcoholic steatohepatitis Clinical Research Network scoring system.ResultsqSteatosis showed a good correlation with steatosis grade (R: 0.823–0.953, p

PurposeIn this study, the aim was to comprehensively analyze the current status, hotspots, and trends of trans-oral endoscopic thyroidectomy (TOET) through bibliometric analysis and by presenting the field atlas.MethodsWeb of Science Core Collection database was adopted to screen studies regarding TOET published between January 1, 2008 and August 1, 2022. The evaluation covered the criteria total number of studies, keywords, and contributions from countries/regions, institutions, journals, and authors.ResultsA total of 229 studies were covered. SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES is the largest publication in the field of TOET. The three countries that contributed the most studies were Korea, China, and the USA. The most frequently occurring core keywords in the field of TOET are vestibular approach, outcomes, experience, safety, robotic thyroidectomy, scar, video-assisted thyroidectomy and quality-of-life. The seven clusters were generated in this study: intraoperative monitoring of the laryngeal return nerve (# 0), learning curve (# 1), postoperative quality of life (# 2), central lymph node dissection and safety (# 3), complications (# 4), minimally invasive surgery (# 5), and robotic surgery (# 6).ConclusionThe main research topics in the field of TOET place focuses on learning curves, laryngeal nerve monitoring, carbon dioxide gas bolus, chin nerve injury, surgical complications, and surgical safety. In the future, more academics will focus on the safety of the procedure and reducing complications..

Accurately identifying inefficient urban land is essential for urban regeneration and mining underutilized assets. Previous studies have primarily focused on examining the overall efficiency of land use without adequately considering the heterogeneity of urban land use types and comprehensive characteristics of urban quality. As a result, the spatial accuracy and precision of research findings have been relatively low. To address this gap, we developed a comprehensive method to identify inefficient urban lands for residential, commercial, and industrial use. The method integrated multi-source geographic data to quantitatively characterize the efficiency of different land use types considering six key dimensions, including building attribute, urban service, transportation condition, environmental quality, business performance, and production efficiency, utilized principal component analysis to reduce the multicollinearity and the dimensionality of the data, and identified land clusters with similar features that were inefficiently used by means of hierarchical clustering. By applying the method to Changsha, China, we validated its effectiveness. The results demonstrate that the method can accurately identify inefficient residential, commercial, and industrial land, with kappa coefficients of 0.71, 0.77, and 0.68, respectively. The identification results reveal the spatial distribution patterns of different types of inefficient land. Inefficient residential land is concentrated towards the city center, particularly in central areas. Inefficient commercial land is relatively evenly distributed, mainly outside the core commercial regions. Inefficient industrial land clusters towards the periphery, forming several agglomeration areas centered around industrial parks. By precisely identifying inefficient urban land and focusing on the key influencing factors, the proposed method enables the site selection of urban regeneration, site redevelopment evaluation, and optimization of urban resources.

Hashimoto’s thyroiditis (HT) is the main cause of hypothyroidism. Here the authors develop a deep learning model for diagnosis of HT on a large multi-site dataset including image and video data.

Objective: Large volume radiological text data have been accumulated since the incorporation of electronic health record (EHR) systems in clinical practice. We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis. Methods: Sonographic EHR data were obtained from the EHR database. Pathological reports were used as the gold standard for diagnosing thyroid cancer. We developed thyroid cancer diagnosis based on natural language processing (THCaDxNLP) to interpret unstructured sonographic text reports for thyroid cancer diagnosis. We used the area under the receiver operating characteristic curve (AUROC) as the primary metric to measure the performance of the THCaDxNLP. We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs. those without THCaDxNLP using 5 independent test sets. Results: We obtained a total number of 788,129 sonographic radiological reports. The number of thyroid sonographic data points was 132,277, 18,400 of which were thyroid cancer patients. Among the 5 test sets, the numbers of patients per set were 439, 186, 82, 343, and 171. THCaDxNLP achieved high performance in identifying thyroid cancer patients (the AUROC ranged from 0.857–0.932). Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy (93.8% vs. 87.2%; one-sided t-test, adjusted P = 0.003), precision (92.5% vs. 86.0%; P = 0.018), and F1 metric (94.2% vs. 86.4%; P = 0.007). Conclusions: THCaDxNLP achieved a high AUROC for the identification of thyroid cancer, and improved the accuracy, sensitivity, and precision of thyroid ultrasound radiologists. This warrants further investigation of THCaDxNLP in prospective clinical trials.

Abstract BAR (Bin/Amphiphysin/Rvs) domain containing proteins function as lipid bilayer benders and curvature sensors, and they contribute to membrane shaping involved in cell signaling and metabolism. The mechanism for their membrane shape sensing has been investigated by both equilibrium binding and kinetic studies. In prior research, stopped-flow spectroscopy has been used to deduce a positive dependence on membrane curvature for the binding rate constant, k on , of a BAR protein called endophilin. However, the impact of bulk diffusion of endophilin, on the kinetic binding parameters has not been thoroughly considered. Employing similar methods, and using lipid vesicles of multiple sizes, we obtained a linear dependence of k on on vesicle curvature. However, we found that the observed relation can be explained without considering the local curvature sensing ability of endophilin in the membrane association process. In contrast, the diffusion-independent unbinding rate constant (k off ) obtained from stopped-flow measurements shows a negative dependence on membrane curvature, which is controlled/mediated by endophilin-membrane interactions. This latter dependency, in addition to protein–protein interactions on the membrane, explains the selective binding of BAR proteins to highly curved membranes in equilibrium binding experiments.

Objective: To evaluate the obstetrical and oncological progression of twin pregnancies with hydatidiform mole coexisting fetus (HMCF). Materials and methods: Using a retrospective method based on patients from the Women's Hospital, Zhejiang University School of Medicine database between January 1990 and October 2020, 17 patients were histologically confirmed as having HMCF, and the patients' prenatal diagnosis, outcomes and development of gestational trophoblastic neoplasia (GTN) were reviewed. Results: Among these 17 cases, 11 (64.71%) cases were complete hydatidiform mole coexisting fetus (CHMCF), and 6 (35.29%) cases were partial hydatidiform mole coexisting fetus (PHMCF). The gestational age at diagnosis of CHMCF was significantly earlier than that of PHMCF [9 (8–24) vs. 18 (11–32) weeks, respectively, P