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Abstract Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, enabling efficient determination of structures at near-atomic resolutions. However, a common challenge arises from the severe imbalance among various conformations of vitrified particles, leading to low-resolution reconstructions in rare conformations due to a lack of particle images in these quasi-stable states. We introduce CryoTRANS, a method that predicts high-resolution maps of rare conformations by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions. This trajectory is represented by an ordinary differential equation parameterized by a deep neural network, ensuring retention of detailed structures from high-resolution density maps. By leveraging a single high-resolution density map, CryoTRANS significantly improves the reconstruction of rare conformations and has been validated on four real-world datasets: alpha-2-macroglobulin, actin-binding protein complexes, SARS-CoV-2 spike glycoprotein, and the 70S ribosome. CryoTRANS can also predict high-resolution structures in cryogenic electron tomography maps using a high-resolution cryo-EM map.

With the development of the Internet, the number of electronic texts has increased rapidly. Automatic grammar error correction technology is an effective safeguard measure for the quality of electronic texts. To improve the quality of electronic text, this study introduces a moving window algorithm and linear interpolation smoothing algorithm to build a Cn-gram language model. On this basis, a syntactic analysis strategy is introduced to construct a syntactic error correction model integrating Cn-gram and syntactic analysis, and English grammar intelligent error correction is carried out through the model. The results show that compared with the Bi-gram and Tri-gram, the precision of the Cn-gram model is 0.85 and 0.91% higher, and the F1 value is 0.97 and 1.14% higher, respectively. Compared with the results of test set Long, the Cn-gram model has better performance on verb error correction of the Short test set, and the precision rate, recall rate, and F1 value are increased by 0.86, 3.94, and 1.87%, respectively. The comparison of the precision, recall rate, and F1 value of the proposed grammar error correction model on the complete test set shows that the precision of the study is 19.10 and 5.41% higher for subject–verb agreement errors. The recall rate is 9.55 and 10.77% higher, respectively; F1 values are higher by 12.65 and 10.59%, respectively. The above results show that the error-correcting technique of the research design has excellent error-correcting performance. It is hoped that this experiment can provide a reference for the relevant research of automatic error correction technology of electronic text.

Abstract Background At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer. Methods 171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups. Results All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p 0.05) and postoperative respiratory complications (P > 0.05). Conclusions The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.

Air cargo is an important component of transportation and plays a vital role in the efficient allocation of high-quality resources on global and regional scales. Air cargo contributes significantly to regional economic development by strengthening inter-regional cooperation and resource integration. However, air cargo geography has received relatively less attention from the research community. Existing studies have analyzed the spatial pattern of air cargo using a limited cross-sectional data from selected years, lacking an analysis of its influencing factors. Based on spatial statistics and panel data of air cargo, this study explores the evolution process and characteristics of China's air cargo pattern on a 20-years time scale and quantitatively reveals its key influencing factors. The research findings are as follows: 1) Air cargo in China has transitioned from the rapid development stage to the stable development stage in the past 20 years; 2) Air cargo volume in China is mainly concentrated in the eastern region, and in the past 20 years, China's air cargo center of gravity has been generally located at the junction of Anhui, Henan, and Hubei provinces, showing a spatial displacement trend from Henan to Anhui to Hubei; 3) The pattern of air cargo network in China remains relatively stable, forming a rhombic structure with Beijing, Shanghai, Guangzhou, and Shenzhen as the core; 4) Air cargo development in China is influenced by factors such as urban scale, industrial structure, and ground transportation development. Among them, urban economy, transportation, warehousing, postal and telecommunications industry, and technological investment have a significant positive impact on air cargo volume, whereas the wholesale and retail trade industries have a significant negative impact. For air logistics hubs, the influencing factors are consistent with those of the entire sample airport. However, for non-aviation logistics hubs, population size and research and technology services have a significant positive impact, whereas ground transportation accessibility has a significant negative impact. This study enriches the long-term time-series analysis and quantitative research content in the field of air cargo and has significance for the development of air transportation geography and the construction of a strong civil aviation industry in China.

Transverse myelitis is the second most common symptoms in myelin oligodendrocyte antibody-associated diseases (MOGAD), causing obvious clinical manifestation. T2-hyperintense lesions mainly restricted to the gray matter in the spinal cord on axial magnetic resonance imaging, produce the H-sign, which is thought to be the typical finding of MOGAD. Contrast enhancement can be observed in some cases of myelin oligodendrocyte antibody-associated transverse myelitis (MOG-TM). However, reports on the enhancement pattern associated with the H-sign are rarely seen. In this report, we describe a case of pediatric MOG-TM in which the H-sign was observed without enhancement, while the surrounding white matter exhibited enhancement. This pattern contradicts the previously observed gray matter involvement. Then we reviewed the literatures of myelin oligodendrocyte antibody-positive myelitis to focus on the neuroimaging features and discuss the implications of our finding.

Abstract Identifying potential prognostic factors of CSM patients could improve doctors’ clinical decision-making ability. The study retrospectively collected the baseline data of population characteristics, clinical symptoms, physical examination, neurological function and quality of life scores of patients with CSM based on the clinical big data research platform. The modified Japanese Orthopedic Association (mJOA) score and SF-36 score from the short-term follow-up data were entered into the cluster analysis to characterize postoperative residual symptoms and quality of life. Four clusters were yielded representing different patterns of residual symptoms and quality of patients’ life. Patients in cluster 2 (mJOA RR 55.8%) and cluster 4 (mJOA RR 55.8%) were substantially improved and had better quality of life. The influencing factors for the better prognosis of patients in cluster 2 were young age (50.1 ± 11.8), low incidence of disabling claudication (5.0%) and pathological signs (63.0%), and good preoperative SF36-physiological function score (73.1 ± 24.0) and mJOA socre (13.7 ± 2.8); and in cluster 4 the main influencing factor was low incidence of neck and shoulder pain (11.7%). We preliminarily verified the reliability of the clustering results with the long-term follow-up data and identified the preoperative features that were helpful to predict the prognosis of the patients. This study provided reference and research basis for further study with a larger sample data, extracting more patient features, selecting more follow-up nodes, and improving clustering algorithm.

Abstract Introduction As a novel internal fixation for femoral neck fractures, the femoral neck system has some advantages for young Pauwels type III femoral neck fractures without clear biomechanical effects and mechanisms. Thus, the objection of the study is to realize the biomechanical effects and mechanism of FNS cannulated screws on treating young patients with Pauwels type III femoral neck fractures compared to cannulated screws which are commonly used for femoral neck fractures by finite element analysis. Methods Firstly, the model of young Pauwels type III femoral neck fractures, femoral neck system (FNS), and three cannulated screws (CS) arranged in an inverted triangle were established, and the internal fixations were set up to fix young Pauwels type III femoral neck fractures. Under 2100 N load, the finite element was performed, and the deformation, peak von Mises stress (VMS), and contact at fracture segments were recorded to analyze the biomechanical effects and mechanism of FNS and three-CS fixing young Pauwels type III femoral neck fractures. Results Compared to three-CS, the deformation of the whole model, internal fixation, and fracture segments after FNS fixation were lower, and the peak VMS of the whole model and the internal fixation after FNS were higher with lower peak VMS of the distal femur and the fracture segments. With a sticking contact status, the contact pressure at fracture segments after FNS fixation was lower than that of three-CS. Conclusions FNS can provide better mechanical effects for young patients with Pauwels type III femoral neck fractures, which may be the mechanical mechanism of the clinical effects of FNS on femoral neck fracture. Although there is high stress on FNS, it is still an effective and safe internal fixation for young patients with Pauwels type III femoral neck fractures.

Abstract Topography is an important factor affecting soil erosion and is measured as a combination of the slope length and slope steepness (LS-factor) in erosion models, like the Chinese Soil Loss Equation. However, global high-resolution LS-factor datasets have rarely been published. Challenges arise when attempting to extract the LS-factor on a global scale. Furthermore, existing LS-factor estimation methods necessitate projecting data from a spherical trapezoidal grid to a planar rectangle, resulting in grid size errors and high time complexity. Here, we present a global 1-arcsec resolution LS-factor dataset (DS-LS-GS1) with an improved method for estimating the LS-factor without projection conversion (LS-WPC), and we integrate it into a software tool (LS-TOOL). Validation of the Himmelblau–Orlandini mathematical surface shows that errors are less than 1%. We assess the LS-WPC method on 20 regions encompassing 5 landform types, and R2 of LS-factor are 0.82, 0.82, 0.83, 0.83, and 0.84. Moreover, the computational efficiency can be enhanced by up to 25.52%. DS-LS-GS1 can be used as high-quality input data for global soil erosion assessment.

Abstract Objectives To evaluate the clinical and non-contrast computed tomography (CT) features of patients with benign pulmonary subsolid nodules (SSNs) with a solid component ≤ 5 mm and their development trends via follow-up CT. Methods We retrospectively collected 436 data from patients who had SSNs with a solid component ≤ 5 mm, including 69 with absorbable benign SSNs (AB-SSNs), 70 with nonabsorbable benign SSNs (NB-SSNs), and 297 with malignant SSNs (M-SSNs). Models 1, 2, and 3 for distinguishing the different types of SSNs were then developed and validated. Results Patients with AB-SSNs were younger and exhibited respiratory symptoms more frequently than those with M-SSNs. The frequency of nodules detected during follow-up CT was in the following order: AB-SSNs > NB-SSNs > M-SSNs. NB-SSNs were smaller than M-SSNs, and ill-defined margins were more frequent in AB-SSNs than in NB-SSNs and M-SSNs. Benign SSNs exhibited irregular shape, target sign, and lower CT values more frequently compared to M-SSNs, whereas the latter demonstrated bubble lucency more commonly compared to the former. Furthermore, AB-SSNs showed more thickened interlobular septa and satellite lesions than M-SSNs and M-SSNs had more pleural retraction than AB-SSNs (all p

Categorised as a directed energy deposition process, wire arc additive manufacturing (WAAM) is a promising technology for fabricating large-scale structures and components across various industries. However, the quality of WAAM parts depends on the tool trajectory, as it affects the temperature distribution. Ideally, temperature-related issues, such as overheating, are minimised by choosing an optimal deposition sequence. Selecting the deposition sequence solely on intuition is an unreliable approach, particularly when dealing with complex and irregular parts. This paper introduces a simplified WAAM simulation (SWS) model, which was embedded into an optimisation procedure for determining the optimal deposition sequence of thin-walled WAAM parts. The proposed method is based on a semi-analytical function, which was calibrated and validated using thermal histories obtained from finite element simulations. The findings showed that the proposed SWS model can reproduce the average thermal history at predefined positions within a sample part with minimal computational effort. Moreover, the optimisation successfully identified optimal deposition sequences for producing the sample part regarding a given optimisation criterion. The outcomes of this research contribute to the tool trajectory planning process for WAAM parts. An optimal deposition sequence improves WAAM part quality, increasing the usability of WAAM technology in the production industry.

Background: The long-term prognosis for patients with osteosarcoma (OS) metastasis remains unfavourable, highlighting the urgent need for research that explores potential biomarkers using innovative methodologies. Methods: This study explored potential biomarkers for OS metastasis by analysing data from the Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases. The synthetic minority oversampling technique (SMOTE) was employed to tackle class imbalances, while genes were selected using four feature selection algorithms (Monte Carlo feature selection [MCFS], Borota, minimum-redundancy maximum-relevance [mRMR], and light gradient-boosting machine [LightGBM]) based on the gene expression matrix. Four machine learning (ML) algorithms (support vector machine [SVM], extreme gradient boosting [XGBoost], random forest [RF], and k-nearest neighbours [kNN]) were utilized to determine the optimal number of genes for building the model. Interpretable machine learning (IML) was applied to construct prediction networks, revealing potential relationships among the selected genes. Additionally, enrichment analysis, survival analysis, and immune infiltration were performed on the featured genes. Results: In DS1, DS2, and DS3, the IML algorithm identified 53, 45, and 46 features, respectively. Using the merged gene set, we obtained a total of 79 interpretable prediction rules for OS metastasis. We subsequently conducted an in-depth investigation on 39 crucial molecules associated with predicting OS metastasis, elucidating their roles within the tumour microenvironment. Importantly, we found that certain genes act as both predictors and differentially expressed genes. Finally, our study unveiled statistically significant differences in survival between the high and low expression groups of TRIP4, S100A9, SELL and SLC11A1, and there was a certain correlation between these genes and 22 various immune cells. Conclusions: The biomarkers discovered in this study hold significant implications for personalized therapies, potentially enhancing the clinical prognosis of patients with OS.

Abstract The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

A series of palladium-modified (Pd-modified) CuO-ZnO-Al2O3 (CZA) catalysts with various Pd loadings (0.3 wt% to 2.4 wt%) were prepared using the wetness impregnation method, on two CZA supports with different structures that are CZA-aged precursor composed of a mixture of zincian-malachite and hydrotalcite-like phases (CZA-zH), and CuO-ZnO-Al2O3 metal oxide nanoparticles (CZA-MO). Enhancement on catalytic activity can be observed on both Pd-modified CZA catalysts in a temperature range of 180–240 °C for methanol synthesis via CO2 hydrogenation. Pd/CZA-zH catalysts exhibited a more efficient and stable production of methanol at a relatively low reaction temperature of 180 °C for 100 hrs of reaction. The improvement of activity is mainly ascribed to a higher surface area and abundant oxygen-containing functional groups (e.g., –OH) of CZA-zH support, which is beneficial for better adsorption and distribution of Pd promoter. Hydrogen temperature programmed reduction and X-ray photoelectron spectroscopy results demonstrated a better interaction between Pd and Cu on Pd/CZA-zH catalysts via enhanced reducibility of CuO, and peak shift of Cu to a lower binding energy. The difference in the efficient utilization of hydrogen spillover effect of Pd promoter over two CZA supports resulted in the different performances for methanol synthesis under mild reaction conditions.

Abstract High‐fat diet (HFD)‐induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity‐associated human lncRNA LINK‐A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD‐induced obesity knock‐in (KI) mouse model. Mechanistically, HFD LINK‐A KI mice induce the infiltration of inflammatory factors, including IL‐1β and CXCL16, through the LINK‐A/HB‐EGF/HIF1α feedback loop axis in a self‐amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK‐A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK‐A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD‐induced obesity and metabolic syndrome, pointing out LINK‐A as a valuable and effective therapeutic target for treating HFD‐induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK‐A) in remodeling tissue inflammatory microenvironments to promote HFD‐induced obesity.

Abstract Introduction How to reconstruct the damaged fingertip is a clinical problem. Our team propose the theory of equivalent design and use the mini toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique to reconstruct Allen’s type II fingertip injury. Thus, we perform the retrospective study to evaluate the effects of this technique on fingertip injury. Materials and methods A retrospective analysis was performed on 56 patients admitted to our hospital from January 2015 to January 2020 who used equivalently designed miniature hallux toenail flaps for the plastic repair of fingertip damage. We recorded the size of the miniature hallux toenail flap, operation time, intraoperative blood loss, and complications and calculated the survival rate of the transplanted miniature hallux toenail flap. During routine follow-up after surgery, we recorded nail growth time and observed finger appearance. At the last time of follow-up, we recorded Semmes-Weinstein evaluating tactile sensation and Two-point discrimination testing (TPD). The efficacy was evaluated by Zook score evaluation. Results The size of the mini hallux toenail flap was 0.71 cm × 1.22 cm to 0.88 cm × 1.71 cm. The operation time was (3.54 ± 0.58) hours, the intraoperative blood loss was (20.66 ± 4.87) ml, and the survival rate of mini hallux toenail flaps was 100%. The postoperative follow-up time was (30.82 ± 11.21) months, and the total nail growth time was (9.68 ± 2.11) months. The average tactile sensation evaluated by the Semmes-Weinstein test was (0.32 ± 0.14) g, and the average TPD was (7.33 ± 1.02) mm. According to Zook score, the curative effect of fifty-six cases were all excellent or good with 100% excellent and good rate, and all patients had beautiful appearances and good function of damaged fingertips. Conclusions Based on the equivalent design theory, the mini hallux toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique is an effective method to reconstruct Allen’s type II fingertip injury with a beautiful appearance and good function. Type of study/level of evidence Therapeutic IV.

Abstract Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Nav1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Nav1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Nav1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated “wedged” position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself.

Abstract Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals’ behavioral and psychological well-being during and after confinement periods. Here, we analyze China’s five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming “digital residents.” This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.

Abstract Voltage-gated sodium (Nav) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in structural elucidation of Nav channels, the binding mode of most Nav-targeting drugs remains unknown. Here we report high-resolution cryo-EM structures of human Nav1.7 treated with drugs and lead compounds with representative chemical backbones at resolutions of 2.6-3.2 Å. A binding site beneath the intracellular gate (site BIG) accommodates carbamazepine, bupivacaine, and lacosamide. Unexpectedly, a second molecule of lacosamide plugs into the selectivity filter from the central cavity. Fenestrations are popular sites for various state-dependent drugs. We show that vinpocetine, a synthetic derivative of a vinca alkaloid, and hardwickiic acid, a natural product with antinociceptive effect, bind to the III-IV fenestration, while vixotrigine, an analgesic candidate, penetrates the IV-I fenestration of the pore domain. Our results permit building a 3D structural map for known drug-binding sites on Nav channels summarized from the present and previous structures.

Abstract Background Patients with insulo-Sylvian gliomas continue to present with severe morbidity in cognitive functions primarily due to neurosurgeons’ lack of familiarity with non-traditional brain networks. We sought to identify the frequency of invasion and proximity of gliomas to portions of these networks. Methods We retrospectively analyzed data from 45 patients undergoing glioma surgery centered in the insular lobe. Tumors were categorized based on their proximity and invasiveness of non-traditional cognitive networks and traditionally eloquent structures. Diffusion tensor imaging tractography was completed by creating a personalized brain atlas using Quicktome to determine eloquent and non-eloquent networks in each patient. Additionally, we prospectively collected neuropsychological data on 7 patients to compare tumor-network involvement with change in cognition. Lastly, 2 prospective patients had their surgical plan influenced by network mapping determined by Quicktome. Results Forty-four of 45 patients demonstrated tumor involvement (

Abstract Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.

The application of orthopedic implants for bone tissue reconstruction and functional restoration is crucial for patients with severe bone fractures and defects. However, the abiotic nature of orthopedic implants allows bacterial adhesion and colonization, leading to the formation of bacterial biofilms on the implant surface. This can result in implant failure and severe complications such as osteomyelitis and septic arthritis. The emergence of antibiotic-resistant bacteria and the limited efficacy of drugs against biofilms have increased the risk of orthopedic implant-associated infections (OIAI), necessitating the development of alternative therapeutics. In this regard, antibacterial hydrogels based on bacteria repelling, contact killing, drug delivery, or external assistance strategies have been extensively investigated for coating orthopedic implants through surface modification, offering a promising approach to target biofilm formation and prevent OIAI. This review provides an overview of recent advancements in the application of antibacterial hydrogel coatings for preventing OIAI by targeting biofilm formation. The topics covered include: (1) the mechanisms underlying OIAI occurrence and the role of biofilms in exacerbating OIAI development; (2) current strategies to impart anti-biofilm properties to hydrogel coatings and the mechanisms involved in treating OIAI. This article aims to summarize the progress in antibacterial hydrogel coatings for OIAI prevention, providing valuable insights and facilitating the development of prognostic markers for the design of effective antibacterial orthopedic implants.

Oxidative stress (OS) plays a pivotal role in the pathogenesis of spinal cord injury (SCI), yet its underlying mechanisms remain elusive. In this study, we explored the OS phenotype in a rat model of SCI. Subsequently, comprehensive bioinformatic analyses were conducted on microarray data pertaining to SCI (GSE45006). Notably, KEGG enrichment analysis revealed a pronounced enrichment of pivotal pathways, namely MAPK, FoxO, Apoptosis, NF-κB, TNF, HIF-1, and Chemokine across distinct phases of SCI. Furthermore, GO enrichment analysis highlighted the significance of biological processes including response to hypoxia, response to decrease oxygen levels, response to reactive oxygen species, cellular response to oxidative stress, reactive oxygen species metabolic process, and regulation of neuron death in the context of OS following SCI. Notably, our study underscores the prominence of nine genes, namely Itgb1, Itgam, Fn1, Icam1, Cd44, Cxcr4, Ptprc, Tlr4, and Tlr2 as OS key genes in SCI, consistently expressed in both the acute phase (1, 3, 7 days) and sub-acute phase (14 days). Subsequently, the relative mRNA expression of these key genes in different time points (1, 3, 7, 14 days) post-SCI. Finally, leveraging the DsigDB database, we predicted ten potential compounds potentially targeting OS and facilitating the repair of SCI, thus providing novel insights into the mechanisms underlying OS and identifying potential therapeutic targets for SCI.

Abstract The BiS2‐based layered superconductors with structures similar to those of cuprates and iron‐based superconductors have stimulated much research interest. Here, a new quaternary compound is reported, Bi5O4S3Cl, which crystalizes in a tetragonal structure with P4/mmm (No. 123) space group having alternately stacking unique BiS3 layers and Bi2O2 layers along the c‐axis with a Cl atom located at the center of the unit cell. A superconducting transition above 3 K is observed for both electrical transport and magnetic measurements. Hall resistivity measurements show its multiband character with a conduction dominated by electron‐like charge carriers. The first‐principles calculations exhibit that the semiconducting parent phase Bi5O4S3Cl becomes metallic when sulfur vacancies are introduced, which hints the origin of superconductivity in Bi5O4S3Cl. The findings will inspire the exploration of new BiS‐based superconductors.

Synchrotron radiation based dynamic micro-computed tomography (micro-CT) is a powerful technique available at synchrotron light sources for investigating evolving microstructures. Wet granulation is the most widely used method of producing pharmaceutical granules, precursors to products like capsules and tablets. Granule microstructures are known to influence product performance, so this is an area for potential application of dynamic CT. Here, lactose monohydrate (LMH) was used as a representative powder to demonstrate dynamic CT capabilities. Wet granulation of LMH has been observed to occur on the order of several seconds, which is too fast for lab-based CT scanners to capture the changing internal structures. The superior X-ray photon flux from synchrotron light sources makes sub-second data acquisition possible and well suited for analysis of the wet-granulation process. Moreover, synchrotron radiation based imaging is non-destructive, does not require altering the sample in any way, and can enhance image contrast with phase-retrieval algorithms. Dynamic CT can bring insights to wet granulation, an area of research previously only studied via 2D and/or ex situ techniques. Through efficient data-processing strategies, dynamic CT can provide quantitative analysis of how the internal microstructure of an LMH granule evolves during the earliest moments of wet granulation. Here, the results revealed granule consolidation, the evolving porosity, and the influence of aggregates on granule porosity.

Visualization of low-density tissue scaffolds made from hydrogels is important yet challenging in tissue engineering and regenerative medicine (TERM). For this, synchrotron radiation propagation-based imaging computed tomography (SR-PBI-CT) has great potential, but is limited due to the ring artifacts commonly observed in SR-PBI-CT images. To address this issue, this study focuses on the integration of SR-PBI-CT and helical acquisition mode (i.e. SR-PBI-HCT) to visualize hydrogel scaffolds. The influence of key imaging parameters on the image quality of hydrogel scaffolds was investigated, including the helical pitch (p), photon energy (E) and the number of acquisition projections per rotation/revolution (Np), and, on this basis, those parameters were optimized to improve image quality and to reduce noise level and artifacts. The results illustrate that SR-PBI-HCT imaging shows impressive advantages in avoiding ring artifacts with p = 1.5, E = 30 keV and Np = 500 for the visualization of hydrogel scaffolds in vitro. Furthermore, the results also demonstrate that hydrogel scaffolds can be visualized using SR-PBI-HCT with good contrast while at a low radiation dose, i.e. 342 mGy (voxel size of 26 µm, suitable for in vivo imaging). This paper presents a systematic study on hydrogel scaffold imaging using SR-PBI-HCT and the results reveal that SR-PBI-HCT is a powerful tool for visualizing and characterizing low-density scaffolds with a high image quality in vitro. This work represents a significant advance toward the non-invasive in vivo visualization and characterization of hydrogel scaffolds at a suitable radiation dose.

The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses.

Abstract Ischemic vascular disease is a major healthcare problem. The keys to treatment lie in vascular regeneration and restoration of perfusion. However, current treatments cannot satisfy the need for vascular regeneration to restore blood circulation. As biomedical research has evolved rapidly, a variety of potential alternative therapeutics has been explored widely, such as growth factor-based therapy, cell-based therapy, and material-based therapy including nanomedicine and biomaterials. This review will comprehensively describe the main pathogenesis of vascular injury in ischemic vascular disease, the therapeutic function of the above three treatment strategies, the corresponding potential challenges, and future research directions.

Glycerol flux across the plasma membrane is critical to metabolism and linked to disease. Here, authors present the cryo-EM structure of the glycerol channel AQP7 composed of two adhering tetramers and displaying well-defined densities in the central pore.

The Yungang Grottoes, excavated during the 5th to 6th centuries AD, stand as a pinnacle of Buddhist sculpture, representing a precious world cultural heritage. Since their excavation, the grottoes have undergone multiple phases of painting, with a significant amount of pigment still present on the surfaces of the stone carvings. Since the 1990s, two large-scale archaeological excavations have been conducted on both the front ground and the summit of Yungang Grottoes. During these excavations, various artifacts with accompanying pigments were unearthed, encompassing stone carvings, grinding tools, architectural components, fragments of murals, and remnants of clay sculptures, spanning the historical periods of the Northern Wei, Liao-Jin, and Ming-Qing dynasties. Using portable X-ray fluorescence spectrometry, portable microscopy, polarizing microscopy, scanning electron microscopy–energy dispersive X-ray spectroscopy, and confocal Raman microscopy, we conducted a comprehensive analysis of these painted elements. The investigation revealed the presence of hematite, vermilion, goethite, malachite, calcium carbonate, lead white, and ivory black pigments in the Northern Wei samples. The Liao-Jin samples exhibited hematite, while the Ming-Qing samples contained vermilion, minium, atacamite, lead white, and Prussian blue.

The presence of young stars, aged around several million years and situated within the range of ∼0.04–1 pc from our Galactic center raises a question about their origins and dynamical evolutions. Their kinematics provide an opportunity to explore their formation or possible subsequent dynamical evolution. If Sagittarius A* was active in the past as suggested by several observations, the accretion disk may have a significant impact on the dynamics of stars in the Galactic center. The drag force exerted on stars during star–disk interaction could lead some of them to sink into the accretion disk, and these embedded stars will rapidly migrate inward and eventually be disrupted within ∼10 ^5 yr. This could roughly explain the absence of stars within 2.5 × 10 ^4 R _g (∼1000 au). Additionally, Kozai–Lidov oscillations, induced by the gravitational perturbation of the disk, could contribute to the bimodal distribution of S-star inclinations and drive a majority of stars into high-eccentricity orbits.

Weak-line quasars (WLQs) are a notable group of active galactic nuclei (AGNs) that show unusually weak UV lines even though their optical-UV continuum shapes are similar to those of typical quasars. The physical mechanism for WLQs is an unsolved puzzle in the AGN unified model. We explore the properties of UV emission lines by performing extensive photoionization calculations based on Cloudy simulations with different spectral energy distributions (SEDs) of AGNs. The AGN continua are built from several observational empirical correlations, where the blackbody emission from the cold disk, the power-law emission from the hot corona, and a soft X-ray excess component are considered. We find that the equivalent width (EW) of C iv from our models is systematically lower than observational values if the component of soft X-ray excess is neglected. The EW will increase several times and is roughly consistent with the observations after considering the soft X-ray excess component as constrained from normal type I AGNs. We find that the UV lines are weak for QSOs with quite large black hole mass (e.g., M _BH > 10 ^9 M _⊙ ) and weak soft X-ray emission due to the deficit of ionizing photons. As an example, we present the strength of C iv based on the multiband SEDs for three nearby weak-line AGNs, where the weaker soft X-ray emission normally predicts the weaker lines.

Summary: The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE.For complete details on the use and execution of this protocol, please refer to Wang et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ObjectivesIn adult diffuse glioma, preoperative detection of isocitrate dehydrogenase (IDH) status helps clinicians develop surgical strategies and evaluate patient prognosis. Here, we aim to identify an optimal machine-learning model for prediction of IDH genotyping by combining deep-learning (DL) signatures and conventional radiomics (CR) features as model predictors.MethodsIn this study, a total of 486 patients with adult diffuse gliomas were retrospectively collected from our medical center (n=268) and the public database (TCGA, n=218). All included patients were randomly divided into the training and validation sets by using nested 10-fold cross-validation. A total of 6,736 CR features were extracted from four MRI modalities in each patient, namely T1WI, T1CE, T2WI, and FLAIR. The LASSO algorithm was performed for CR feature selection. In each MRI modality, we applied a CNN+LSTM–based neural network to extract DL features and integrate these features into a DL signature after the fully connected layer with sigmoid activation. Eight classic machine-learning models were analyzed and compared in terms of their prediction performance and stability in IDH genotyping by combining the LASSO–selected CR features and integrated DL signatures as model predictors. In the validation sets, the prediction performance was evaluated by using accuracy and the area under the curve (AUC) of the receiver operating characteristics, while the model stability was analyzed by using the relative standard deviation of the AUC (RSDAUC). Subgroup analyses of DL signatures and CR features were also individually conducted to explore their independent prediction values.ResultsLogistic regression (LR) achieved favorable prediction performance (AUC: 0.920 ± 0.043, accuracy: 0.843 ± 0.044), whereas support vector machine with the linear kernel (l-SVM) displayed low prediction performance (AUC: 0.812 ± 0.052, accuracy: 0.821 ± 0.050). With regard to stability, LR also showed high robustness against data perturbation (RSDAUC: 4.7%). Subgroup analyses showed that DL signatures outperformed CR features (DL, AUC: 0.915 ± 0.054, accuracy: 0.835 ± 0.061, RSDAUC: 5.9%; CR, AUC: 0.830 ± 0.066, accuracy: 0.771 ± 0.051, RSDAUC: 8.0%), while DL and DL+CR achieved similar prediction results.ConclusionIn IDH genotyping, LR is a promising machine-learning classification model. Compared with CR features, DL signatures exhibit markedly superior prediction values and discriminative capability.

ObjectiveThis meta-analysis aimed to compare the relative safety and efficacy of cannulated compression screw (CCS) and femoral neck system (FNS) in treating patients with femoral neck fractures and to provide evidence-based medical evidence for FNS in treating femoral neck fractures.MethodsPubMed, Embase, Cochrane, and China National Knowledge Infrastructure databases were searched to collect outcomes related to femoral neck fractures treated with FNS and CCS, including time to fracture healing, incidence of non-union, incidence of osteonecrosis of the femoral head, incidence of failure of internal fixation, rate of femoral neck shortening, Harris hip score, Barthel index, operative time, intraoperative blood loss, fluoroscopy frequency, and complications. A meta-analysis was performed using RevManv5.4 (The Cochrane Collaboration) and Stata v14.0 software.ResultsThis analysis included 21 studies involving 1,347 patients. The results showed that FNS was superior to CCS in terms of fracture healing time [mean difference (MD) = −0.75, 95% CI = (−1.04, −0.46), P 0.05], Harris hip score [MD = 3.31, 95% CI = (1.99, 4.63), P

The status and role of airport agglomeration in China's airport system is becoming increasingly important, and air transport networks have received attention from multidisciplinary fields such as transportation planning, transport geography, and transport economics. Based on the analysis of the structural characteristics of airport agglomeration in China's air transport network, this study innovatively constructs an evaluation framework for the co-opetition relationship of airport agglomeration with the help of graph theory, set theory, and industrial economics theoretical methods. Considering the topological connectivity and weighted strength of connected airports, this study establishes a quantitative evaluation model for the co-opetition relationship of the airport agglomeration's air transport network from the perspectives of the overall and interactive markets. The Guangdong-Hong Kong-Macao Greater Bay Area's airport agglomeration is a world-class airport agglomeration with the largest aviation traffic volume and a relatively mature market in China. Three large airports, Guangzhou (CAN), Hong Kong (HKG), and Shenzhen (SZX), occupy the leading positions in the Greater Bay Area. In recent years, the air transport network of the Guangdong-Hong Kong-Macao Greater Bay Area's airport agglomeration has mainly expanded to medium- and long-distance routes. With the construction-based evaluation method, we found the following: (1) From the perspective of overall market competition index, the co-opetition market of airport agglomeration in the Greater Bay Area is dominated by a complete monopoly market and a weak cooperative market. In 2019, the complete monopoly market accounted for 33.8%, a decrease of 4.1% compared with 2015. The market with weak cooperation accounted for 42.3%, and market share remained relatively stable. The market with weak competition accounted for 15.8% of the market, and the market share remained relatively stable. The market with strong competition accounted for 6.3%, a decrease of 4.5% from 2015. Based on the calculation and analysis of the weighted strength of connected airports, there are significant differences in the co-opetition indices of similarly connected airports. The level of competition in the overall market has intensified. (2) From the perspective of interactive competition, the interactive co-opetition market within the airport group in the Greater Bay Area is dominated by strong and weak cooperation markets. From the co-opetition index of airports connecting with the Greater Bay Area, there are ten pairs of airports belonging to the strong cooperation markets in 2019, i.e. between Guangzhou and Huizhou, Macau and Foshan, Hongkong and Zhuhai airports, a decrease of six compared with 2015. The weak cooperation markets in 2019 included ten pairs of airports, such as Guangzhou and Hong Kong, Hong Kong and Shenzhen, Macau and Huizhou, an increase of six pairs of airports compared with 2015. Based on the weighted strength of connected airports, this study analyzes the interactive competition patterns. In 2019, the strong cooperation markets included eight pairs of airports, including Guangzhou-Foshan, Guangzhou-Huizhou, and Hong Kong-Huizhou, a decrease of two pairs compared with 2015. The weak cooperation markets include eight pairs of airports, such as Guangzhou-Macau, Hong Kong-Shenzhen, and Macau-Shenzhen, a decrease of two pairs compared with 2015. The weak competitive markets include four pairs of airports, namely, Guangzhou-Hong Kong, Hong Kong-Macau, and Shenzhen-Zhuhai, an increase in three pairs of airports compared with 2015. In general, the co-opetition market pattern of the Greater Bay Area turns from a cooperative overall to a competitive transformation.

Voltage-gated Ca2+ channel subtype Cav2.3 represents a potential drug target for neurological diseases. Here, authors report cryo-EM structures of Cav2.3 and its mutant to reveal the crosstalk of intracellular segments, which may facilitate future drug discovery.

Abstract Background Situs inversus totalis (SIT) is a relatively rare congenital abnormality in which the major thoracic and abdominal visceral organs are reversed from their usual positions. In patients with SIT and bronchial carcinoma, surgical difficulty increases sharply. It has been reported that the video-assisted thoracic surgery (VATS) still poses the operator to a challenge situation. The similarity of surgical positions and the flexibility of the mechanical arm in robotic surgery, may be beneficial to SIT patients due to reducing technical difficulties. Here, we present a first case of SIT patient with lung cancer, in which Da Vinci robot-assisted thoracic surgery (RATS) was performed successfully. Case presentation A 66-year old patient, previously diagnosed with SIT since childhood, came to our hospital with two pulmonary nodules in his left lung field. The bigger one had increased somewhat for the last 2 years of follow-up. Software Mimics was preoperatively carried out to analyze anatomical variations. RATS was conducted to complete left upper lobectomy and left middle wedge resection. The patient had no intraoperative complications and was discharged day 5 after the operation. Conclusions This is the first report of a successful robot-assisted lung cancer resection in a patient with SIT. In such challenging cases as lung cancer and rare anomaly as SIT, RATS is more advantageous and suitable than VATS with the help of software Mimics utilized for 3D reconstruction, which can identify the anatomical abnormalities and facilitate the surgical procedures.

Abstract Background Accurate diagnosis of unexplained cervical lymphadenopathy (CLA) using medical images heavily relies on the experience of radiologists, which is even worse for CLA patients in underdeveloped countries and regions, because of lack of expertise and reliable medical history. This study aimed to develop a deep learning (DL) radiomics model based on B-mode and color Doppler ultrasound images for assisting radiologists to improve their diagnoses of the etiology of unexplained CLA. Methods Patients with unexplained CLA who received ultrasound examinations from three hospitals located in underdeveloped areas of China were retrospectively enrolled. They were all pathologically confirmed with reactive hyperplasia, tuberculous lymphadenitis, lymphoma, or metastatic carcinoma. By mimicking the diagnosis logic of radiologists, three DL sub-models were developed to achieve the primary diagnosis of benign and malignant, the secondary diagnosis of reactive hyperplasia and tuberculous lymphadenitis in benign candidates, and of lymphoma and metastatic carcinoma in malignant candidates, respectively. Then, a CLA hierarchical diagnostic model (CLA-HDM) integrating all sub-models was proposed to classify the specific etiology of each unexplained CLA. The assistant effectiveness of CLA-HDM was assessed by comparing six radiologists between without and with using the DL-based classification and heatmap guidance. Results A total of 763 patients with unexplained CLA were enrolled and were split into the training cohort (n=395), internal testing cohort (n=171), and external testing cohorts 1 (n=105) and 2 (n=92). The CLA-HDM for diagnosing four common etiologies of unexplained CLA achieved AUCs of 0.873 (95% CI: 0.838–0.908), 0.837 (95% CI: 0.789–0.889), and 0.840 (95% CI: 0.789–0.898) in the three testing cohorts, respectively, which was systematically more accurate than all the participating radiologists. With its assistance, the accuracy, sensitivity, and specificity of six radiologists with different levels of experience were generally improved, reducing the false-negative rate of 2.2–10% and the false-positive rate of 0.7–3.1%. Conclusions Multi-cohort testing demonstrated our DL model integrating dual-modality ultrasound images achieved accurate diagnosis of unexplained CLA. With its assistance, the gap between radiologists with different levels of experience was narrowed, which is potentially of great significance for benefiting CLA patients in underdeveloped countries and regions worldwide.

Condensation water can accelerate weathering of stone relics. Previous methods for detecting condensation water in grottoes have some shortcomings, such as the complex equipment layout and limited monitoring range, and are unable to reflect the real-time condensation state, which restrict the effective prevention and control of condensation water in grottoes. In this paper, the infrared thermal imaging technology, which can be used to obtain continuous and large-scale observation of temperature on the wall of grottoes, and the microwave moisture measurement technology, which can be used to obtain rock moisture inside the wall, are both used to study the formation mechanism of condensation water. During the occurrence of a rainfall event, a wall in cave 19 of the Yungang Grottoes was monitored by the infrared thermal imaging for 100 hours. This set of data reveals the diurnal variation pattern of temperature before and during the rainfall event, and two periods beneficial for the formation of condensation water were identified by comparing with the air dew point temperature. The two periods are the condensation period before cooling which starts from 16 hours before rainfall to a sudden drop of temperature during rainfall and the condensation period after cooling which starts from the sudden drop of temperature to 12 hours after the end of rainfall. At the same time, the dynamic monitoring of the shallow rock moisture content for 56 hours was carried out with a microwave moisture meter. Although condensation water cannot be directly observed on the wall, the microwave moisture meter shows that water content in the rock increases, indicating that water has been preferentially condensed inside the rock. It is also found that the sudden drop of air temperature (from 18.5 °C to 15.6 °C in 1 hour) during the process of rainfall causes the condensation of water vapor in atmosphere, which causes a significant decline in the dew point temperature, and the condition of condensation water formation is not fulfilled. This phenomenon is of important guiding significance for the prevention and control of condensation water.

Background: Few study has investigated how paraspinal muscle endurance deteriorates in lumbar spinal stenosis (LSS) patients. In addition, little information is available on the relationship between clinical outcomes and the endurance of paraspinal muscles. Objective: To explore the correlation between paraspinal extensor muscle endurance, quality of life (QOL) and sagittal spinopelvic alignment. Besides, we attempted to propose a paraspinal extensor muscle endurance test (PEMET) classification for identifying the severity of clinical symptoms and sagittal imbalance in LSS patients. Methods: 171 hospitalized LSS patients and 100 healthy controls from the community were prospectively enrolled in this study. The paraspinal extensor endurance test was performed at baseline according to Ito test. The LSS patients were stratified into three groups based on the performance time of endurance test: grade I (60s). Clinical measures of QOL included the visual analog scale scores (VAS) for back pain and leg pain and the Oswestry Disability Index (ODI). Sagittal alignment was analysed by standing posteroanterior and lateral whole spine X-ray in LSS patients. Results: The LSS group had a significantly shorter performance time of the endurance test than the control group. The paraspinal muscle endurance significantly correlated with VAS-back, VAS-leg, ODI, pelvic tilt, lumbar lordosis and sagittal vertical axis (SVA; all p 40; p = 0.005, OR = 0.985) and global sagittal imbalance (SVA >50 mm; p = 0.019, OR = 0.985). Based on PEMET classification, moving from the grade III group to the grade I group, there was progressive worsening in VAS-back and ODI (all adjusted p

BackgroundSpinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury.ObjectiveTo investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI.MethodsWe searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria.ResultsResults revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92–2.87, p

ObjectiveThis study aimed to compare the clinical, radiological, therapeutic, and prognostic differences between pediatric patients showing acute disseminated encephalomyelitis (ADEM) with and without myelin oligodendrocyte glycoprotein (MOG) antibodies.MethodsWe retrospectively collected all available data of children diagnosed with ADEM and tested for serum MOG antibodies at the Children's Hospital of Chongqing Medical University from January 2017 to May 2021.ResultsA total of 62 patients were included in our cohort, of which 35 were MOG-seropositive and 27 were MOG-seronegative. MOG-seropositive ADEM children presented with significantly lower rates of seizures (P = 0.038) and cranial nerve (III–XII) palsy (P = 0.003). Isolated leukocytosis in the blood was more common in ADEM children with MOG antibodies (P < 0.001). The two groups showed no significant differences in the distributions and extent of the MRI lesions as well as the appearance of typical/atypical magnetic resonance imaging (MRI) features. MOG-seropositive children were more likely to relapse (P = 0.017) despite having slower oral prednisolone tapering after acute treatments (P = 0.028). In scoring performed on the basis of two neurological function scoring systems, MOG-seropositive children showed milder neurological disability status at onset (P = 0.017 and 0.025, respectively) but showed no difference during follow-up.ConclusionIn summary, the differences in the clinical manifestations and auxiliary examination findings for MOG-seropositive and MOG-seronegative ADEM children lacked significance and specificity, making early identification difficult. MOG-seropositive children were more likely to relapse and showed slower steroid tapering. Moreover, MOG-seronegative children tended to have more severe neurological impairments at onset with no difference during follow-up.

Abstract Objective The structural alteration that occurs within the salience network (SN) in patients with insular glioma is unclear. Therefore, we aimed to investigate the changes in the topological network and brain structure alterations within the SN in patients with insular glioma. Methods We enrolled 46 patients with left insular glioma, 39 patients with right insular glioma, and 21 demographically matched healthy controls (HCs). We compared the topological network, gray matter (GM) volume, and fractional anisotropy (FA) between HCs and patients after controlling for the effects of age and gender. Results Patients with insular glioma showed topological network decline mainly in the insula, basal ganglia region, and anterior cingulate cortex (ACC). Compared with HCs, patients primarily showed GM volume increased in the ACC, inferior temporal gyrus (ITG), superior temporal gyrus (STG), temporal pole: middle temporal gyrus (TPOmid), insula, middle temporal gyrus (MTG), middle frontal gyrus, and superior occipital gyrus (SOG), but decreased in TPOmid, ITG, temporal pole: superior temporal gyrus, and SOG. FA declined mainly in the STG, MTG, ACC, superior frontal gyrus, and SOG, and also showed an increased cluster in SOG. Conclusions FA represents the integrity of the white matter. In patients with insular glioma, decreased FA may lead to the destruction of the topological network within the SN, which in turn may lead to the decrease of network efficiency and brain function, and the increase of GM volume may compensate for these changes. Overall, this pattern of structural changes provides new insight into the compensation model of insular glioma.

SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50–400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin) increased in a dose-dependent manner, whereas the bone resorption marker (β-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR-1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dose-dependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP.

In this paper, the finite-time trajectory tracking control problem of a flexible link manipulator (FLM) system with unknown parameters is investigated in joint space. An adaptive nonsingular terminal sliding mode (ANTSM) controller based on an extended state observer (ESO) is proposed to ensure that the tracking error converges to a small neighborhood of zero. Firstly, an adaptive ESO is introduced, which is used to estimate unknown system parameters, including the unknown rigid-flexible coupling coefficient and the unknown control gain. Then, an ESO based on the parameters estimated above is proposed to estimate the unmodeled dynamics and external disturbances of the system in real-time. Finally, an ANTSM controller based on ESO is studied to achieve finite-time trajectory tracking control and vibration suppression without any prior knowledge of system uncertainties and external disturbances. The finite-time convergence ability of the closed-loop system is proved by Lyapunov theory. Experimental results on the Quanser Flexible Link System verify the effectiveness of the proposed controller.

Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug.

The projected ocean acidification (OA) associated with increasing atmospheric CO2 alters seawater chemistry and hence the bio-toxicity of metal ions. However, it is still unclear how OA might affect the long-term resilience of globally important marine microalgae to anthropogenic metal stress. To explore the effect of increasing pCO2 on copper metabolism in the diatom Thalassiosira pseudonana (CCMP 1335), we employed an integrated eco-physiological, analytical chemistry, and transcriptomic approach to clarify the effect of increasing pCO2 on copper metabolism of Thalassiosira pseudonana across different temporal (short-term vs. long-term) and spatial (indoor laboratory experiments vs. outdoor mesocosms experiments) scales. We found that increasing pCO2 (1,000 and 2,000 μatm) promoted growth and photosynthesis, but decreased copper accumulation and alleviated its bio-toxicity to T. pseudonana. Transcriptomics results indicated that T. pseudonana altered the copper detoxification strategy under OA by decreasing copper uptake and enhancing copper-thiol complexation and copper efflux. Biochemical analysis further showed that the activities of the antioxidant enzymes glutathione peroxidase (GPX), catalase (CAT), and phytochelatin synthetase (PCS) were enhanced to mitigate oxidative damage of copper stress under elevated CO2. Our results provide a basis for a better understanding of the bioremediation capacity of marine primary producers, which may have profound effect on the security of seafood quality and marine ecosystem sustainability under further climate change.

Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy.Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved.Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels.Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1β and TNF-α) by LPS-induced RAW264.7 macrophages (p < .01).Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

Abstract Background In clinical practice, a number of delayed diagnoses of localized pneumonic-type lung adenocarcinoma (L-PLADC) mimicking pneumonia have been identified due to the lack of knowledge regarding the radiological findings associated with this condition. Here, we defined L-PLADC as a special type of lung adenocarcinoma that presents as a focal consolidation involving