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Purpose: The objective of the present study was to determine the accuracy of T-scan system and Cerec Omnicam system with respect to the evaluation of occlusal contact by quantitatively comparing the occlusal contact areas and the overlapping ratios of occlusal contact areas obtained from these systems. Material and methods: The occlusal contact of 20 adolescents with normal occlusion was measured with the T-scan system and the Cerec Omnicam system, respectively. The occlusal contact areas in the intercuspal position were then quantified with Adobe Photoshop CS6 Software. The same procedure was repeated for each subject using with 8 μm articulating paper as the control group. The overlapping ratio of T-scan system and Cerec Omnicam system was calculated respectively, which is defined as the ratio of overlapping areas comparing with those obtained from articulating paper. To examine the accuracy of T-scan system and Cerec Omnicam system, the Paired t-test was applied. The reproducibility of T-scan system was evaluated with Wilcoxon matched-pairs signed-ranks test by comparing the occlusal contact areas between two repeated measurements. In all statistical analysis, the level of significance was set to α = 0.05. Results: Results demonstrated measured occlusal contact areas were significantly different between those obtained between T-scan system and Cerec Omnicam system (P

BackgroundClostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD) and has been reported as a risk factor for poor outcome. However, gut microbiome and mycobiome of IBD patients with CDI have been barely investigated. This study aimed to assess the gut microbiome and mycobiome in IBD patients with CDI.MethodsWe collected fecal samples from patients with active IBD and concomitant CDI (IBD-CDI group, n=25), patients with active IBD and no CDI (IBD-only group, n=51), and healthy subjects (HC, n=40). Patients’ characteristics including demographic data, disease severity, and medication history were collected. Metagenomic sequencing, taxonomic and functional analysis were carried out in the samples.ResultsWe found that the bacterial alpha diversity of the IBD-CDI group was decreased. The bacterial and fungal beta diversity variations between IBD patients and HC were significant, regardless of CDI status. But the IBD-CDI group did not significantly cluster separately from the IBD-only group. Several bacterial taxa, including Enterococcus faecium, Ruminococcus gnavus, and Clostridium innocuum were overrepresented in the IBD-CDI group. Furthermore, IBD patients with CDI were distinguished by several fungal taxa, including overrepresentation of Saccharomyces cerevisiae. We also identified functional differences in IBD patients with CDI include enrichment of peptidoglycan biosynthesis. The network analysis indicated specific interactions between microbial markers in IBD-CDI patients.ConclusionIBD patients with CDI had pronounced microbial dysbiosis. Gut micro-ecological changes in IBD patients with CDI might provide insight into the pathological process and potential strategies for diagnosis and treatment in this subset of patients.

ObjectiveTo explore the corrective effect of 6 degree of freedom couch on rotation errors in intensity modulated radiotherapy (IMRT) for postoperative rectal cancer patients, further to probe into the clinical application value of 6 degree of freedom couch in radiotherapy.MethodsFrom January 1, 2020 to December 1, 2020, 30 patients with rectal cancer receiving postoperative intensity modulated radiotherapy in The First Hospital of Hebei Medical University were included in this retrospective study. The setup error values in all direction of patients before and after 6 degree of freedom correction were collected during each radiotherapy session.ResultsIn this study, a total of 382 data before and after the correction of 6 degree of freedom couch were collected. It was found that the setup errors in the Y direction gradually increased, was maximal in the third week, and then became smaller, and the setup errors in the other directions increased with the extension of radiotherapy time and reached the maximum at the 5th week. In the translation direction, the setup errors value in Z direction occurred more frequently than that in X and Y directions between the range of 0.21-0.80 cm. In the rotation direction, the setup errors value in rotation X direction occurred more frequently than that in rotation Y and Z directions between the range of 0.21°-2.99°. In addition, after the correction of the 6 degree of freedom couch in real time, the setup errors in patients were significantly reduced in all directions (P < 0.05).ConclusionIn summary, it was recommended to clinically use 6 degree of freedom couch combined with IMRT for real-time correction of placement errors in patients with rectal cancer undergoing radiotherapy. At the same time, it was necessary to observe the tumor size and body weight changes of patients on the 5th week. If necessary, radiotherapy positioning and planning should be performed in time.

Aptamer (Apt) is a kind of recognition molecule with excellent affinity and high specificity. Transmembrane glycoprotein mucin (MUC1) is an important tumor biomarker overexpressed in MCF-7 tumor cells. MUC1 Apt (Apt-M) could specifically target MCF-7 tumor cells. Ti3C2 nanosheets with high photothermal conversion efficiency were considered as a promising therapeutic nanoplatform for tumor therapy. Doxorubicin (DOX) is a common anti-tumor drug. Herein, a novel DOX/Ti3C2/Apt-M therapeutic nanoplatform was successfully fabricated, which could specifically target MCF-7 tumor cells. As expected, the temperature of DOX/Ti3C2/Apt-M therapeutic nanoplatform raised rapidly under laser irradiation. Meanwhile, chemotherapy was triggered through multimodal stimuli-responsive drug release from the DOX/Ti3C2/Apt-M therapeutic nanoplatform under acidic environment and laser-induced local high temperature. Encouragingly, the MCF-7 cell viability of DOX/Ti3C2/Apt-M with laser irradiation was only 26.9%. The tumor surface temperature of MCF-7 xenograft mice in the DOX/Ti3C2/Apt-M + Laser group rose to about 58.3 °C, which was significantly higher than other laser irradiation groups. The experiments in vitro and in vivo indicated that the DOX/Ti3C2/Apt-M therapeutic nanoplatform can rapidly accumulate in MCF-7 tumors with excellent active targeting properties, and display superior tumor suppressive ability through combination therapy. This work provides a new idea of targeted tumor therapy based on Ti3C2 nanosheets.

Summary: Aberrant minichromosome maintenance (MCM) expression is associated with tumorigenesis. Here, we performed immunohistochemistry integrated with digital pathology to identify MCM2/5/6 expression in 130 neuroblastoma patients. A risk score was established using least absolute shrinkage and selection operator that predicts outcomes according to MCM2 expression, age, and the International Neuroblastoma Staging System in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset (n = 150), where the patients with high risk had significantly worse prognosis that was validated in a hospital-based cohort (n = 130). After multivariable adjustment, the risk model remained an independent factor for survival in the TARGET cohort (overall survival [OS]: hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4–4.0; event-free survival [EFS]: HR 1.8, 95% CI 1.1–3.1) and for OS in the validation cohort (HR 8.3, 95% CI 1.6–44.5). The ESTIMATE indicates that the risk model is negatively correlated with low ESTIMATE and stromal scores. These findings show the additive nature of this score, fostering its future implementation with new prognostic variables.

Abstract With the advantages of superior energy density, lithium‐sulfur batteries (LSBs) have been considered as one of the promising next‐generation batteries. However, some key issues, such as the shuttle effect of the intermediate lithium polysulfides, poor conductivity of the sulfur, Li2S and Li2S2, and huge volume variation during charge/discharge process, have hindered its development. In this respect, a variety of nanomaterials have been used to overcome the above‐mentioned defects. Among them, two‐dimensional (2D) nanomaterials present unique merits for enhancing the electrochemical performance of LSBs owing to their unique structural properties. Nevertheless, the variation of 2D nanomaterials used in LSBs is rarely discussed. Herein, this work systematically reviews the state‐of‐the‐art progress in LSB cathode development through 2D materials such as graphene, MXenes, 2D compounds, and so forth. With a comprehensive analysis, the challenges and perspectives for 2D nanomaterials in LSBs application are proposed and discussed.

Bridge operational accident analysis is a critical process in bridge operational risk management. It provides valuable knowledge support for responding to newly occurring accidents. However, there are three issues: (1) research specifically focused on the past bridge operational accidents is relatively scarce; (2) there is a lack of mature research findings regarding the bridge operational accidents knowledge representation; and (3) in similar case retrieval, while case-based reasoning (CBR) is a valuable approach, there are still some challenges and limitations associated with its usage. To tackle these problems, this research proposed an automated analysis approach for bridge operational accidents based on a knowledge graph and CBR. The approach includes case representation and case retrieval, leveraging advancements in computer science and artificial intelligence. In the proposed approach, the case representation involves the adoption of a knowledge graph to construct multi-dimensional networks. The knowledge graph captures the relationships between various factors and entities, allowing for a comprehensive representation of accidents domain knowledge. In the case retrieval, a multi-circle layer retrieval strategy was innovatively proposed to enhance retrieval efficiency. Three target cases were randomly selected to verify the validity of the proposed methodology. The combination of a knowledge graph and CBR can indeed provide useful tools for the automated analysis of bridge operational accidents. Additionally, the proposed methodology can serve as a reference for intelligent risk management in other types of infrastructures.

Driving pattern has been increasingly researched to improve driving safety and develop autonomous vehicles. Oriented towards the complex infrastructures at signalized intersections, this research digs into the risk sources brought by different kinds of road elements, including road lane markings, road curbs, median separators, signal timing, and neighboring vehicles around the ego car. Referring to vehicle speed both in the longitudinal and latitudinal dimensions, risk scope and distribution are quantified with the vehicle position of a torus with a Gaussian cross-section. Then, the risk is summed over all the road elements across all the points involved by the ego car, the level of which should be controlled within the threshold value when the ego vehicle explores to minimize trip delay. Thus, autonomous driving strategies are developed with respect to vehicle speed and steering angle. The proposed model is validated with NGSIM data, where a signalized intersection on Peachtree Street is selected and vehicles moving in different directions are analyzed. It is found that the proposed model manages to control vehicles with risk at the accepted level and to enhance the speed level as well as reduce acceleration fluctuations. This research contributes to improving autonomous driving against complex driving conditions for driving safety and efficiency.

Background. The measurement and analysis of clinical crowns play a crucial role in stomatology, anthropology, and studies of genetic and environmental variables in oral and maxillofacial development. Purpose. The objective of the present study was to measure the parameters of clinical crowns of permanent dentition in youth of Han nationality using intraoral scanning and identify potential influencing factors. Materials and Methods. A total of 100 subjects (50 males and 50 females) of Han nationality aged 18–24 with normal occlusion were selected. An intraoral scanner was used to obtain the digital dental impressions, and Materialise Magics 21 software was used to measure the mesiodistal diameter (MDD), buccolingual diameter (BLD), height, mesiodistal angle (MDA), and vestibulo-oral angle (VOA) of clinical crowns. The central height was calculated based on the height of clinical crowns. SPSS 27.0 software was used for statistical analysis. The two-independent-samplet-test was used to assess discrepancies in clinical crowns between males and females. The paired t-test was used to determine differences between antimetric pairs of clinical crowns within the same arch. The repeatability of intraoral scanning was tested using the paired t-test between two measurements at one-month intervals. The overall estimated effect was considered significant where P

Accelerated urbanization has increased regional traffic congestion. To alleviate traffic congestion in a homogeneous road network, combined with the advantage of real-time traffic information obtained by the Internet of Vehicles (IoVs), a boundary guidance strategy for traffic congestion region is proposed. The strategy considers the optimal operation state of traffic congestion region and is divided into two categories according to different destinations of traffic demands. Meanwhile, a method for the boundary guidance strategy is presented in which the macroscopic fundamental diagram (MFD) is used to determine the optimal accumulation, a traffic flow equilibrium model is established to calculate the real-time accumulation, and a fuzzy adaptive PID control algorithm is designed to calculate the optimal traffic inflow of the traffic congestion region. Furthermore, an example is selected for simulation. The results show that the boundary guidance strategy can effectively improve the operational state of the road network and alleviate traffic congestion. Finally, the influence of connected vehicle penetration rate on the strategy is discussed. The simulation results show that the strategy can improve the operation state of the road network under mixed traffic flow, and the higher the penetration rate, the more significant its effect on alleviating traffic congestion.

Abstract Background Deep vein thrombosis (DVT) is a vascular disease that has no effective treatment at present. Endothelial cells play a crucial role in the processes vasoconstriction, platelet activation, and blood coagulation and are an integral part of the vascular response to injury resulting in thrombus formation. Objective The aim of this study was to investigate the roles and mechanisms of long noncoding RNA LINC00659 (LINC00659) in endothelial cells. Methods The functions of LINC00659 and miR‐525‐5p on endothelial cells were explored by cell transfection assays, and the expression levels of LINC00659, miR‐525‐5p, and Bax in human umbilical vein endothelial cells (HUVECs) were assessed with reverse transcriptase‐quantitative polymerase chain reaction (RT‐qPCR). Binding sites of LINC00659 and miR‐525‐5p were subsequently analyzed with bioinformatics software, and validated with dual‐luciferase reporter gene assay. Effects of LINC00659 and miR‐525‐5p on proliferation and apoptosis of HUVECs were detected with MTT (3‐(45)‐dimethylthiahiazo (‐z‐y1)‐35‐di‐phenytetrazoliumromide) assay and flow cytometry. RT‐qPCR and western blot analysis were used to evaluate the mRNA and protein levels of apoptosis‐related markers Bcl‐2 and Bax in HUVECs. Results LINC00659 directly targeted and negatively regulated miR‐525‐5p, and Bax was a target of miR‐525‐5p. Upregulation of LINC00659 could inhibit proliferation and promote apoptosis of HUVECs, while the silencing of LINC00659 could increase the viability of HUVECs and inhibit apoptosis via upregulating miR‐525‐5p. Further mechanistic studies revealed miR‐525‐5p could negatively regulate Bax in HUVECs, and increased the viability of HUVECs and inhibited apoptosis by downregulating Bax expression. Conclusion LINC00659 played an important role in DVT by regulating the apoptosis of vascular endothelial cells through regulating miR‐525‐5p/Bax axis.

BackgroundWith changes in the way of life and work, an increasing number of people are suffering from insomnia. In China, a traditional Chinese medicine method tuina is widely used for the treatment of insomnia. However, the evidence for tuina therapy for insomnia remains controversial. Therefore, this systematic review aimed to evaluate the effect of tuina therapy on the symptoms of patients with primary insomnia.MethodsFrom establishment to January 2022, a comprehensive literature search was conducted using seven electronic databases to identify randomized controlled trials of tuina therapy for insomnia. We used RevMan 5.4 software and the GRADEpro Guideline Development Tool to evaluate the quality of the included randomized controlled trials and perform the meta-analysis. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Subgroup analysis was performed according to the different intervention methods. The I2 statistic was used to assess the heterogeneity.ResultsEighteen studies conducted from 2011 to 2021 were included, with a total of 1,471 patients. In terms of efficacy, tuina alone was superior to other treatments [odds ratio (OR), 3.46; 95% confidence interval (CI), 2.15, 5.55; P < 0.00001]; tuina combined with other treatments (acupuncture, scraping, auricular acupuncture, Suanzaoren decoction, estazolam) was more effective than other single therapies (OR, 3.99; 95% CI, 2.84, 5.61; P < 0.00001). In terms of Pittsburgh Sleep Quality Scale score, the improvement in insomnia patients by tuina alone was better than that of other treatments [standardized mean difference (SMD), −2.57; 95% CI, −2.98, −2.17; P < 0.00001], and tuina combined with other treatments (acupuncture, scraping, auricular point pressing, Suanzaoren decoction, estazolam) was better than other single therapies (SMD, −2.83; 95% CI, −2.98, −2.68; P < 0.00001).ConclusionThis meta-analysis revealed that tuina can significantly improve the clinical efficacy and sleep quality of patients with primary insomnia. This study provides a theoretical basis and treatment guidance for patients with primary insomnia.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022355742.

Conventional machine vision systems suffer from great data latency and energy consumption in cognitive tasks due to the separated vision sensors, memory units, and processors. In‐sensor computing based on optoelectronic synapses allows efficient computation by directly sensing and processing optical signals. Herein, an optoelectronic synapse based on Au/ZnO:N/IGZO/TiN structure is proposed. It shows uniform optical SET and electrical RESET behaviors, with various light‐tunable plasticity. Furthermore, a 4‐bit reservoir is experimentally implemented on the device, which is ideal to construct in‐sensor reservoir computing (RC) system. By converting spatiotemporal optical signals to higher dimensional feature space, in‐sensor RC has a great advantage in processing sequential visual information. Simulation results demonstrate that the in‐sensor RC system based on the proposed synapse achieves a considerable recognition accuracy (90.45%) for the MNIST dataset with very limited 36‐30‐10 perceptron network, and a 97.14% accuracy for human action classification from sequential vision data based on the Weizmann dataset. This work proves the low training cost and great efficiency for processing spatiotemporal and sequential optical signals, which may pave a new way for future machine vision applications.

Abstract The memristive stateful logic can realize the memory and computation, thus effectively avoid the huge time and energy overhead caused by data moving between memory and computation units. However, the memristive stateful logic still faces the reliability challenges caused by the variability of memristor, which prevents it from practical applications. A reliability reinforcement method with low overhead in delay, area and peripheral circuits is thus needed to be studied urgently. This paper proposes a novel method of reliability reinforcement based on logic gates' margin. By optimizing circuit structure and driving voltage configuration, the margin of logic gates is improved to tolerant memristors' variability to the maximum extent, and thus reinforces logic gates' reliability. Simulations demonstrate that the proposed method can improve the allowed threshold variability range by 42% and 92% for 2‐input NAND gate and 2‐input OR gate, respectively. Benchmark with other methods shows that the proposed margin‐based reinforcement method achieves almost the same reliability reinforcement effect, but the overhead in area and peripheral circuit is greatly reduced.

Silk fibroin has been widely used in biological fields due to its biocompatibility, mechanical properties, biodegradability, and safety. Recently, silk fibroin as a drug carrier was developed rapidly and achieved remarkable progress in cancer treatment. The silk fibroin-based delivery system could effectively kill tumor cells without significant side effects and drug resistance. However, few studies have been reported on silk fibroin delivery systems for antitumor therapy. The advancement of silk fibroin-based drug delivery systems research and its applications in cancer therapy are highlighted in this study. The properties, applications, private opinions, and future prospects of silk fibroin carriers are discussed to understand better the development of anti-cancer drug delivery systems, which may also contribute to advancing silk fibroin innovation.

The requirements and the fl exible and reconfi gurable network architecture for the space-integrated-ground information network was proposed based on analyzed the 6G network vision and challenges faced by the space-integrated-ground information network.Based on the proposed network architecture, the intelligent network management and control architecture and the virtualization technology of the space-integrated-ground information network were proposed to realized the dynamic confi gurability of the network.

Abstract Background Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma. Methods Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts. Results Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts. Conclusion The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

In arthroscopic shoulder surgery, general anesthesia (GA) is the common method of anesthesia. Recently, the combined usage of interscalene brachial plexus block with general anesthesia (ISB/GA) was reported to have a lower incidence of adverse side effects than GA alone. However, to date, no study has compared stress and inflammatory responses between these two methods. Since stress and inflammatory responses are critical on intraoperative management and postoperative recovery, we integrated the laboratory and clinical methods and compared the stress and inflammatory factors, such as epinephrine, norepinephrine, glucose, lactate, inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), as well as the clinical outcomes to determine whether ISB/GA provides an advantage on stress and inflammatory inhibition. Data showed that ISB/GA resulted in significantly lower epinephrine, norepinephrine, and glucose levels perioperatively. Six hours after operation, the TNF-α and IL-6 levels were also significantly lower in the ISB/GA group. ISB/GA patients had lower blood pressure, a more stable heart rate, lower visual analog scale score, and less opioid consumption during and after surgery. Our results indicate that ISB/GA is a better choice for arthroscopic shoulder surgery, owing to less stress and inflammatory responses during and after operation, which provides better clinical outcomes. Therefore, we recommend ISB/GA as a preferred anesthesia method for arthroscopic shoulder surgery.

Abstract Liver development is a highly complex process that is regulated by the orchestrated interplay of epigenetic regulators, transcription factors, and microRNAs (miRNAs). Owing to the lack of global in vivo targets of all miRNAs during liver development, the mechanisms underlying the dynamic control of hepatocyte differentiation by miRNAs remain elusive. Here, using Argonaute (Ago) high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse liver at different developmental stages, we characterized massive Ago-binding RNAs and obtained a genome-wide map of liver miRNA-mRNA interactions. The dynamic changes of five clusters of miRNAs and their potential targets were identified to be differentially involved at specific stages, a dozen of high abundant miRNAs and their epigenetic regulation by super-enhancer were found during liver development. Remarkably, miR-122, a liver-specific and most abundant miRNA in newborn and adult livers, was found by its targetome and pathway reporter analyses to regulate the Hippo pathway, which is crucial for liver size control and homeostasis. Mechanistically, we further demonstrated that miR-122 negatively regulates the outcomes of the Hippo pathway transcription factor TEAD by directly targeting a number of hippo pathway regulators, including the coactivator TAZ and a key factor of the phosphatase complex PPP1CC, which contributes to the dephosphorylation of YAP, another coactivator downstream of the Hippo pathway. This study identifies for the first time the genome-wide miRNA targetomes during mouse liver development and demonstrates a novel mechanism of terminal differentiation of hepatocytes regulated by the miR-122/Hippo pathway in a coordinated manner. As the Hippo pathway plays important roles in cell proliferation and liver pathological processes like inflammation, fibrosis, and hepatocellular carcinoma (HCC), our study could also provide a new insight into the function of miR-122 in liver pathology.

Abstract Lithium metal batteries (LMBs) are considered the most promising energy storage devices for applications such as electrical vehicles owing to its tremendous theoretical capacity (3860 mAh g−1). However, the serious safety issues and poor cycling performance caused by the dendritic crystal growth during deposition are concerned for any rechargeable batteries with a lithium metal anode. To make widespread adoption a possibility, considerable efforts have been devoted to suppressing lithium (Li) dendrite growth. In this review, the recent strategies to developing dendrite free Li anode, including constructing an artificial solid electrolyte interface, current collector modification, separator film improvement, and electrolyte additive, are summarized. The merits and shortcomings for different strategies are reviewed and a general summary and perspective on the next generation rechargeable batteries are presented.

In this study, we developed a novel on-line solid phase extraction (SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites (methamphetamine, amphetamine, morphine, codeine, 6-monoacetylmorphine, benzoylecgonine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, cocaine, ketamine, norketamine, and methcathinone) and cotinine (COT) in wastewater samples. The analysis was performed by loading 2 mL of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step (5% methanol) to eliminate interference with a total run time of 13 min. The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process. Typical analytical characteristics used for method validation were sensitivity, linearity, precision, repeatability, recovery, and matrix effects. The limit of detection (LOD) and limit of quantification (LOQ) of each target were set at 0.20 ng/L and 0.50 ng/L, respectively. The linearity was between 0.5 ng/L and 250 ng/L, except for that of COT. The intra- and inter-day precisions were

In the creative design of mechanical devices，the isomorphic kinematic chains should be eliminated to reduce the mechanism scheme for subsequent design and improve the design efficiency of mechanical device. A new method for isomorphism recognition of kinematic chains is proposed based on the Hamming matrix. Firstly，the Hamming matrix of kinematic chains is educed from the link adjacency matrix，then the square matrix of Hamming matrix and the cubic matrix of link adjacency matrix are integrable to obtain the product matrix of kinematic chains. Secondly，the elements of each row in the product matrix are ordered in descending to get the row sequences of the product matrix. Finally，the isomorphism recognition code (IRC) of the kinematic chain is obtained by the sum of the product of the element in the row sequence with the defined topological factor. The isomorphism recognition code does not change with the link labels，so if the isomorphism recognition codes of the kinematic chains are the same，they are isomorphic，otherwise they are not. The effectiveness of this method is proved by a large number of examples. Because of its simplicity，efficiency and convenience for computer execution，it can be considered as a new option for isomorphism screening.

Abstract Small ubiquitin-related modifier (SUMO) proteins are involved in the development of tumors. Ubiquitin-like modifier-activating enzyme 2 (UBA2) is an important member of the SUMO modification system; however, its role in clear cell renal cell carcinoma (ccRCC) is unclear. Therefore, we investigated the expression and function of UBA2 in ccRCC. Both mRNA and protein expression levels of UBA2 were found to be higher in ccRCC than in normal renal tissues and significantly related to the tumor size, Fuhrman grade, and tumor stage. UBA2 knockdown inhibited ccRCC cell growth, promoted apoptosis in vitro and in vivo, and decreased the abundance of a p53 mutant, c-Myc, and key enzymes of the SUMO modification system. Meanwhile, overexpression of UBA2 had the opposite effects. Overexpression of the p53 mutant or c-Myc alleviated the effects of UBA2 knockdown on ccRCC cell proliferation and apoptosis. In conclusion, targeting UBA2 may have a therapeutic potential against ccRCC.

Abstract Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

Abstract Background The imaging features of focal liver lesions (FLLs) are diverse and complex. Diagnosing FLLs with imaging alone remains challenging. We developed and validated an interpretable deep learning model for the classification of seven categories of FLLs on multisequence MRI and compared the differential diagnosis between the proposed model and radiologists. Methods In all, 557 lesions examined by multisequence MRI were utilised in this retrospective study and divided into training–validation (n = 444) and test (n = 113) datasets. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the performance of the model. The accuracy and confusion matrix of the model and individual radiologists were compared. Saliency maps were generated to highlight the activation region based on the model perspective. Results The AUC of the two- and seven-way classifications of the model were 0.969 (95% CI 0.944–0.994) and from 0.919 (95% CI 0.857–0.980) to 0.999 (95% CI 0.996–1.000), respectively. The model accuracy (79.6%) of the seven-way classification was higher than that of the radiology residents (66.4%, p = 0.035) and general radiologists (73.5%, p = 0.346) but lower than that of the academic radiologists (85.4%, p = 0.291). Confusion matrices showed the sources of diagnostic errors for the model and individual radiologists for each disease. Saliency maps detected the activation regions associated with each predicted class. Conclusion This interpretable deep learning model showed high diagnostic performance in the differentiation of FLLs on multisequence MRI. The analysis principle contributing to the predictions can be explained via saliency maps.

In this paper, two near-net-shape continuous casting technologies (strip casting and compact strip production) were used to produce a typical Si–Mn bearing Advanced High Strength Steel (AHSS) slab/strip, aiming to provide a clear understanding on the cooling rate on the solidification structure and corresponding properties. The results showed that strip casting (SC) technology under sub-rapid cooling conditions owns a higher heat transfer efficiency, and the solidified grains have been obviously uniformed and refined. Meanwhile, a substituted quenching process has been completed under high cooling strength of SC, leading the structural transformation from the initial ferrite/pearlite to the composite structure of martensite and bainite, which provides a very good structural basis for the excellent comprehensive mechanical performance of Si–Mn AHSS.

Abstract Objectives Oral lichen planus (OLP) is a T cell-mediated autoimmune disease recognized as an oral potential malignant disorder (OPMD) with the precise mechanism unknown. This study focused on the transcriptional profiles of OLP to elucidate its potential pathogenesis. Methods We conducted RNA sequencing on matched 6 OLP tissues and 6 normal oral mucosal tissues. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and weighted gene co-expression network analysis (WGCNA) were performed on differentially expressed genes (DEGs). We utilized qRT-PCR to validated the top dysregulated genes and hub genes in another 10 pairs of specimens. Results A total of 153 DEGs (p-values

Abstract Studies have shown that matrine has antitumor activity against many types of cancers. However, the direct target in cancer cells of its anticancer effect has not been identified. The purpose of this study was to find the molecular target of matrine to inhibit the proliferation of cancer cells and explore its mechanism of action. Herein we showed that matrine inhibited the proliferation of cancer in vitro and in vivo. Pull-down assay with matrine-amino coupling resins and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) identified Src as the target of matrine. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) provided solid evidences that matrine directly bound to Src. Bioinformatics prediction and pull-down experiment demonstrated that Src kinase domain was required for its interaction with matrine and Ala392 in the kinase domain participated in matrine–Src interaction. Intriguingly, matrine was proven to inhibit Src kinase activity in a non-ATP-competitive manner by blocking the autophosphorylation of Tyr419 in Src kinase domain. Matrine down-regulated the phosphorylation levels of MAPK/ERK, JAK2/STAT3, and PI3K/Akt signaling pathways via targeting Src. Collectively, matrine targeted Src, inhibited its kinase activity, and down-regulated its downstream MAPK/ERK, JAK2/STAT3, and PI3K/Akt phosphorylation signaling pathways to inhibit the proliferation of cancer cells.

Abstract Background Immunotherapy is a valuable option for cancer treatment, and the curative effect of anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobody. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, we explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by administration of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male and female using OLINDA2.1 software. Results 68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPD-L1 or MC38-hPD-L1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3–100 µg in nude mice and approximately 1–100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3–10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15-μg/kg dose was adopted for the PET/CT imaging in the cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, except the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injecting 185 MBq of 68Ga-NOTA-Nb109. Conclusion 68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

Brain computer interface (BCI) is a promising way for automatic driving and exploring brain functions. As the number of electrodes for electroencephalogram (EEG) acquisition continues to grow, the signal processing capabilities of BCI are facing challenges. Considering the bottlenecks of the Von Neumann architecture, it is increasingly difficult for the traditional digital computing pattern to meet the requirements of the EEG signal processing in terms of power consumption and efficiency. Here, we propose a 1T1R array-based EEG signal analysis system in which the biological likelihood of the memristor is used to efficiently analyze signals in the simulated domain. The identification and classification of EEG signals are achieved experimentally using the memristor array with an average recognition rate of 89.83%. The support vector machine classification implemented by the memristor crossbar array provides a 34.4 times improvement in power efficiency compared to the complementary metal oxide semiconductor-based support vector machine classifier. This work provides new ideas for the application of memristors in BCI.

Memristor is a potential basic unit for the in‐memory computing system, which is an approach to break the memory wall of the traditional computer. However, low switching speed, nonuniform device characteristics, and inefficient logic synthesis hinder the development of memristor‐based in‐memory computing. Herein, a novel Cu/α‐Si/α‐C/Pt memristor and direct resistance‐coupling logic synthesis scheme to construct high‐efficiency in‐memory computing is presented. The memristor shows excellent uniformity of low/high resistance (relative dispersion σ/μ = 4.68% and 3.28%) and SET/RESET voltage (relative dispersion σ/μ = 3.24% and 5.85%), fast switching speed (≈30 ns), good endurance (>108), and long retention (>105 s at 100 °C). Complete set of Boolean logic and some derived logic operators are efficiently implemented in the Cu/α‐Si/α‐C/Pt crossbar array. Furthermore, the reconfigurable and parallel logic synthesis is experimentally demonstrated by one‐bit full adder and parallel copy operation. This work can greatly improve the logic computing efficiency and flexibility in the memristor crossbar array.

Abstract Direct electrocatalytic oxidation of benzene has been regarded as a promising approach for achieving high‐value phenol product, but remaining a huge challenge. Here an oxygen‐coordinated nickel single‐atom catalyst (Ni–O–C) is reported with bifunctional electrocatalytic activities toward the two‐electron oxygen reduction reaction (2e− ORR) to H2O2 and H2O2‐assisted benzene oxidation to phenol. The Ni–(O–C2)4 sites in Ni–O–C ar proven to be the catalytic active centers for bifunctional 2e− ORR and H2O2‐assisted benzene oxidation processes. As a result, Ni–O–C can afford a benzene conversion as high as 96.4 ± 3.6% with a phenol selectivity of 100% and a Faradaic efficiency (FE) of 80.2 ± 3.2% with the help of H2O2 in 0.1 m KOH electrolyte at 1.5 V (vs RHE). A proof of concept experiment with Ni–O–C concurrently as cathode and anode in a single electrochemical cell demonstrates a benzene conversion of 33.4 ± 2.2% with a phenol selectivity of 100% and a FE of 44.8 ± 3.0% at 10 mA cm−2.

BackgroundMolecular biomarkers are widely used for disease diagnosis and exploration of pathogenesis. Pulmonary arterial hypertension (PAH) is a rapidly progressive cardiopulmonary disease with delayed diagnosis. Studies were limited regarding molecular biomarkers correlated with PAH from a broad perspective.MethodsTwo independent microarray cohorts comprising 73 PAH samples and 36 normal samples were enrolled in this study. The weighted gene co-expression network analysis (WGCNA) was performed to identify the key modules associated with PAH. The LASSO algorithm was employed to fit a diagnostic model. The latent biology mechanisms and immune landscape were further revealed via bioinformatics tools.ResultsThe WGCNA approach ultimately identified two key modules significantly associated with PAH. For genes within the two models, differential expression analysis between PAH and normal samples further determined nine key genes. With the expression profiles of these nine genes, we initially developed a PAH diagnostic signature (PDS) consisting of LRRN4, PI15, BICC1, PDE1A, TSHZ2, HMCN1, COL14A1, CCDC80, and ABCB1 in GSE117261 and then validated this signature in GSE113439. The ROC analysis demonstrated outstanding AUCs with 0.948 and 0.945 in two cohorts, respectively. Besides, patients with high PDS scores enriched plenty of Th17 cells and neutrophils, while patients with low PDS scores were dramatically related to mast cells and B cells.ConclusionOur study established a robust and promising signature PDS for diagnosing PAH, with key genes, novel pathways, and immune landscape offering new perspectives for exploring the molecular mechanisms and potential therapeutic targets of PAH.

Tumor metastasis is a common event in patients with gastric cancer (GC) who previously underwent curative gastrectomy. It is meaningful to employ high-volume clinical data for predicting the survival of metastatic GC patients. We aim to establish an improved machine learning (ML) classifier for predicting if a patient with metastatic GC would die within 12 months. Eligible patients were enrolled from a Chinese GC cohort, and the complete detailed information from medical records was extracted to generate a high-dimensional dataset. Appropriate feature engineering and feature filter were conducted before modeling with eight algorithms. A 10-fold cross validation (CV) nested in a holdout CV (8:2) was employed for hyperparameter tuning and model evaluation. Model selection was based on the area under the receiver operating characteristic (AUROC) curve, recall, and precision. The selected model was globally explained using interpretable surrogate models. Of the total 399 cases (median survival of 8.2 months), 242 patients survived less than 12 months. The linear discriminant analysis (LDA), support vector machine (SVM), and random forest (RF) model had the highest AUROC (0.78 ± 0.021), recall (0.93 ± 0.031), and precision (0.80 ± 0.026), respectively. The LDA model created a new function that generally separated the two classes. The predicted probability of the SVM model was interpreted using a linear regression model visualized by a nomogram. The predicted class of the RF model was explained using a decision tree model. In summary, analyzing high-volume medical data by ML is helpful to produce an improved model for predicting the survival in patients with metastatic GC. The algorithm should be carefully selected in different practical scenarios.

With the ever-growing demands for sampling rate, conversion resolution, as well as lower energy consumption, the memristor-based neuromorphic analog-to-digital converters (MN-ADC) becomes one of the most potential approaches to break the bottleneck for traditional ADCs. However, the online trainable MN-ADCs are not designed to be easily integrated into the 1T1R crossbar array, meanwhile suffering from the device non-idealities, which makes it difficult to realize high-speed and accurate conversion. To overcome these issues, this paper proposes a high-reliable 2T2R synaptic structure. And through the dedicated structure, we construct a 4-bit MN-ADC that allows for alternate conversions and online adjustments in a single clock period, which can significantly mitigate the effects of device non-idealities on dynamic performance. More importantly, this structure can be perfectly compatible with 1T1R crossbar arrays. Simulation results demonstrate the validity of the proposed MN-ADC, which achieves the ENOB of 3.77 bits, the INL of 0.16 LSB, and the DNL of 0.07 LSB.

BackgroundGiven the mortality benefit of low-dose computed tomography (LDCT) screening on high-risk populations, the retrospective investigation intended to identify the benefits of LDCT on lung cancer screening among the general demographic cohorts.MethodsWe used an opportunistic screening with LDCT implemented during the pandemic in Wuhan to study the impact on subsequent thoracic surgeries, especially surgeries for lung cancer. Patients who received LDCT from October 1, 2019, to July 31, 2020, in three Triple-A accredited hospitals in Wuhan were included in the study. Relative week volumes of both surgeries before and after the chest LDCT screening were compared pairwise. The counts of surgeries for pulmonary nodules or masses, and corresponding pathological results among different gender and age groups were also compared.ResultThe relative weekly volumes of thoracic surgery were significantly greater than those of stomach surgery after the opportunistic screening with LDCT. They were 33% (95% CI, 0.20-0.46; p

Objective To develop and evaluate a psychosocial adaptation (PSA) questionnaire of women with breast cancer treated with adjuvant endocrine therapy (AET).Design Cross-sectional study.Setting Conducted study in a tertiary care centre in China from March to June 2021.Participants Women with breast cancer who have received AET.Methods Item development and extraction were based on literature, qualitative interviews (n=16) and assessment of content validity. 300 participants were recruited to perform item analysis, internal consistency reliability and exploratory factor analysis by cross-sectional studies. Finally, test–retest, criterion validity and confirmatory factor analysis of the questionnaire were performed with 96 respondents.Results An initial questionnaire was devised. The exploratory factor analysis demonstrated four factors: emotional response (six items), self-worth (five items), physical impacts (three items) and social communication (two items). The cumulative contribution of the factors was 65.057%. Cronbach’s alpha coefficient of the questionnaire was 0.876. The correlation coefficient between the questionnaire and General Self-Efficacy Scale was 0.565 (p

Endometriosis is an estrogen-dependent gynecological disease with chronic pelvic inflammation. In order to study the pathophysiology of endometriosis and examine the therapeutic effects of new pharmaceuticals for endometriosis treatment, different animal models had been developed in the last two decades, especially mouse models. However, no study evaluated the effects of various modeling approaches on pathology and immunology in endometriosis. This study aimed to compare endometriotic lesion development and immune profiles under different methods of establishing endometriosis models in mice, including estrus synchronization (ovariectomy with estrogen supplement versus male urine-soaked transfer bedding), endometrium preparations (whole uterus including endometrium and myometrium fragments versus solely endometrium fragments), and surgical transplantation (subcutaneous transplantation versus intraperitoneal injection). Our results showed that lesion growth under estrus synchronization by ovariectomy with estrogen supplement had a higher success rate and more proliferative endometrium, apart from higher body weight gain. Immune responses in peripheral blood were similar in the whole uterus and solely endometrium fragments and in intraperitoneal injection and subcutaneous transplantation, but a more innate immune response in the peritoneal microenvironment was found in solely endometrium fragments and intraperitoneal injection than counterparts. In conclusion, different endometriosis modeling methods result in different pathological and immunological features. Ovariectomy with estrogen supplement, solely endometrium fragments, and intraperitoneal injection are more suitable for both pathological and immunological studies of endometriosis in mice, which are important for mechanistic studies and immunotherapy development.

Craniomaxillofacial (CMF) bone injuries present a major surgical challenge and cannot heal naturally due to their large size and complex topography. We are developing a mineralized collagen scaffold that mimics extracellular matrix (ECM) features of bone. These scaffolds induce in vitro human mesenchymal stem cell (hMSC) osteogenic differentiation and in vivo bone formation without the need for exogenous osteogenic supplements. Here, we seek to enhance pro-regenerative potential via inclusion of placental-derived products in the scaffold architecture. The amnion and chorion membranes are distinct components of the placenta that each have displayed anti-inflammatory, immunomodulatory, and osteogenic properties. While potentially a powerful modification to our mineralized collagen scaffolds, the route of inclusion (matrix-immobilized or soluble) is not well understood. Here we compare the effect of introducing amnion and chorion membrane matrix versus soluble extracts derived from these membranes into the collagen scaffolds on scaffold biophysical features and resultant hMSC osteogenic activity. While inclusion of amnion and chorion matrix into the scaffold microarchitecture during fabrication does not influence their porosity, it does influence compression properties. Incorporating soluble extracts from the amnion membrane into the scaffold post-fabrication induces the highest levels of hMSC metabolic activity and equivalent mineral deposition and elution of the osteoclast inhibitor osteoprotegerin (OPG) compared to the conventional mineralized collagen scaffolds. Mineralized collagen-amnion composite scaffolds elicited enhanced early stage osteogenic gene expression (BGLAP, BMP2), increased immunomodulatory gene expression (CCL2, HGF, and MCSF) and increased angiogenic gene expression (ANGPT1, VEGFA) in hMSCs. Mineralized collagen-chorion composite scaffolds promoted immunomodulatory gene expression in hMSCs (CCL2, HGF, and IL6) while unaffecting osteogenic gene expression. Together, these findings suggest that mineralized collagen scaffolds modified using matrix derived from amnion and chorion membranes represent a promising environment conducive to craniomaxillofacial bone repair.

Dissolved organic matter (DOM) is likely to coexist with microplastics (MPs) in aquatic environments. However, little is known about the effects of different DOM fractions on the stability and aquatic toxicity of MPs. In this study, we separated humic acid (HA) into three molecular weight (MW) fractions (> 30, 3–30, and < 3 k Da) and examined their effects on the toxicity of polyamide 66 (PA66)-MPs to red tilapia (Oreochromis niloticus). Generally, addition of HA enhanced the stability and thus the exposure of tilapia to MPs, leading to the increased accumulation of MPs in the gut, liver, and brain. However, compared with MPs alone, the accumulation of MPs in the gills of tilapia was reduced. Compared with the presence of high-MW HA, the accumulation of MPs in the fish liver was significantly enhanced by 1.1 times in the presence of medium-MW HA (m-HA) after a 10-day exposure. The protein peroxidation on the liver induced by MPs was alleviated by adding all HA fractions. However, compared with MPs alone, the presence of m-HA resulted in a more severe lipid peroxidation, while the presence of low-MW HA alleviate the lipid peroxidation caused by MPs. In addition, the Integrated Biological Responses version 2 (IBRv2) results suggested that the oxidative stress in the liver tilapia caused by MPs could be alleviated by the presence of all HA fractions, which was largely related to the reduced damage caused by lipid peroxidation and/or protein peroxidation. Collectively, our results suggest that the presence of different MW HA fractions could induce complex changes in the MP toxicity on aquatic organisms.

BackgroundSlow walking speed has been shown to predict cognitive decline in older individuals, but studies conducted among Chinese older adults are scarce. We examined the association of walking speed with cognitive function and the trajectory of cognitive decline among Chinese adults aged 60 years and older.MethodsData was from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing nationally representative prospective cohort study. Walking speed was evaluated over a straight 2.5-meter flat course at baseline and categorized into tertiles (the lowest, middle, and highest). Cognitive function was assessed at each wave in three domains: episodic memory, mental status, and global cognition. Data were analyzed using linear mixed-effects models.ResultsA total of 3,954 older adults (48.6% female; mean age: 67.6 ± 5.55 years) were followed for up to 7 years. Participants with lowest walking speed have poorer episodic memory (β = −0.37; 95% CI: −0.46, −0.28), mental status (β = −0.45; 95% CI: −0.60, −0.29), and global cognition (β = −0.81; 95% CI: −1.03, −0.60) over the follow-up. Compared with the highest tertile of walking speed, the lowest walking speed was associated with a faster decline in episodic memory (β = −0.04; 95% CI: −0.07, −0.02), mental status (β = −0.04; 95% CI: −0.07, −0.01), and global cognition (β = −0.06; 95% CI: −0.11, −0.01).ConclusionSlower walking speed is associated with subsequent risk of poorer cognitive function and faster cognitive decline in older Chinese adults.

Identification of the evolution history and genetic diversity of a species is important in the utilization of novel genetic variation in this species, as well as for its conservation. Pistacia chinensis is an important biodiesel tree crop in China, due to the high oil content of its fruit. The aim of this study was to uncover the genetic structure of P. chinensis and to investigate the influence of intraspecific gene flow on the process of domestication and the diversification of varieties. We investigated the genetic structure of P. chinensis, as well as evolution and introgression in the subpopulations, through analysis of the plastid and nuclear genomes of 39 P. chinensis individuals from across China. High levels of variation were detected in the P. chinensis plastome, and 460 intraspecific polymorphic sites, 104 indels and three small inversions were identified. Phylogenetic analysis and population structure using the plastome dataset supported five clades of P. chinensis. Population structure analysis based on the nuclear SNPs showed two groups, clearly clustered together, and more than a third of the total individuals were classified as hybrids. Discordance between the plastid and nuclear genomes suggested that hybridization events may have occurred between highly divergent samples in the P. chinensis subclades. Most of the species in the P. chinensis subclade diverged between the late Miocene and the mid-Pliocene. The processes of domestication and cultivation have decreased the genetic diversity of P. chinensis. The extensive variability and structuring of the P. chinensis plastid together with the nuclear genomic variation detected in this study suggests that much unexploited genetic diversity is available for improvement in this recently domesticated species.

In this study, to optimize the Staphylococcus aureus control program, a meta-analysis was conducted to investigate the epidemiology and antimicrobial resistance (AMR) profile of S. aureus-associated bovine mastitis in China from 2000 to 2020. A total of 33 publications from PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) database were included in our research, among which nine publications included the AMR test. The pooled prevalence of S. aureus was 36.23%, and subgroup analysis revealed that the prevalence dropped from 2000–2010 to 2011–2020, which shows that China is on the right track. The pooled AMR rate indicate isolates were most resistant to β-lactams (50.68%), followed by quinolones (36.23%), macrolides (34.08%), sulfonamides (32.25%), tetracyclines (27.83%), aminoglycosides (26.44%), lincosamides (23.39%), and amphenicol (10.33%). Both the pooled prevalence and AMR of S. aureus in China are higher than those in Western countries, such as Germany, Belgium, Ireland, and the United States—countries with a long animal husbandry history and good management. Thus, there is still room to improve the treatment of S. aureus-associated bovine mastitis in China.

BackgroundThe unknown etiology of sarcoidosis with variable clinical features leads to delayed diagnosis and limited therapeutic strategies. Hence, exploring the latent mechanisms and constructing an accessible and reliable diagnostic model of sarcoidosis is vital for innovative therapeutic approaches to improve prognosis.MethodsThis retrospective study analyzed transcriptomes from 11 independent sarcoidosis cohorts, comprising 313 patients and 400 healthy controls. The weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were performed to identify molecular biomarkers. Machine learning was employed to fit a diagnostic model. The potential pathogenesis and immune landscape were detected by bioinformatics tools.ResultsA 10-gene signature SARDS consisting of GBP1, LEF1, IFIT3, LRRN3, IFI44, LHFPL2, RTP4, CD27, EPHX2, and CXCL10 was further constructed in the training cohorts by the LASSO algorithm, which performed well in the four independent cohorts with the splendid AUCs ranging from 0.938 to 1.000. The findings were validated in seven independent publicly available gene expression datasets retrieved from whole blood, PBMC, alveolar lavage fluid cells, and lung tissue samples from patients with outstanding AUCs ranging from 0.728 to 0.972. Transcriptional signatures associated with sarcoidosis revealed a potential role of immune response in the development of the disease through bioinformatics analysis.ConclusionsOur study identified and validated molecular biomarkers for the diagnosis of sarcoidosis and constructed the diagnostic model SARDS to improve the accuracy of early diagnosis of the disease.

Molecular subtypes of colorectal cancer (CRC) are currently identified via the snapshot transcriptional profiles, largely ignoring the dynamic changes of gene expressions. Conversely, biological networks remain relatively stable irrespective of time and condition. Here, we introduce an individual-specific gene interaction perturbation network-based (GIN) approach and identify six GIN subtypes (GINS1-6) with distinguishing features: (i) GINS1 (proliferative, 24%~34%), elevated proliferative activity, high tumor purity, immune-desert, PIK3CA mutations, and immunotherapeutic resistance; (ii) GINS2 (stromal-rich, 14%~22%), abundant fibroblasts, immune-suppressed, stem-cell-like, SMAD4 mutations, unfavorable prognosis, high potential of recurrence and metastasis, immunotherapeutic resistance, and sensitive to fluorouracil-based chemotherapy; (iii) GINS3 (KRAS-inactivated, 13%~20%), high tumor purity, immune-desert, activation of EGFR and ephrin receptors, chromosomal instability (CIN), fewer KRAS mutations, SMOC1 methylation, immunotherapeutic resistance, and sensitive to cetuximab and bevacizumab; (iv) GINS4 (mixed, 10%~19%), moderate level of stromal and immune activities, transit-amplifying-like, and TMEM106A methylation; (v) GINS5 (immune-activated, 12%~24%), stronger immune activation, plentiful tumor mutation and neoantigen burden, microsatellite instability and high CpG island methylator phenotype, BRAF mutations, favorable prognosis, and sensitive to immunotherapy and PARP inhibitors; (vi) GINS6, (metabolic, 5%~8%), accumulated fatty acids, enterocyte-like, and BMP activity. Overall, the novel high-resolution taxonomy derived from an interactome perspective could facilitate more effective management of CRC patients.

BackgroundEven though the clinical target volume (CTV) in biliary tract cancer (BTC) patients has been proposed by several previous studies, the para aortic CTV for BTC is still not well-defined. The objective of this study was to determine the precise delineation of the para aortic CTV for BTC according to the distribution pattern and failure pattern of lymph nodes.MethodsComputed tomography (CT)-, magnetic resonance imaging (MRI)- or positron emission tomography-computed tomography (PET-CT)-generated images of patients with BTC from 2015 to 2020 were analyzed retrospectively. The distribution patterns of lymph nodes in different regions were summarized. The diagnosed para aortic lymph nodes (PALNs) were manually mapped to standard axial CT images. The asymmetric CTV expansions from the para aortic were defined according to the distance from the volumetric centre of lymph node to the most proximal border of aorta.ResultsA total of 251 positive lymph nodes were found in the study cohort (n = 61 patients, 92 PALN). All PALNs were projected onto axial CT image of the standard patient. PALNs were concentrated in the 16a2 and 16b1 regions, and the involvement rates were 17% and 13% respectively. Therefore, the upper boundary of 16a2 and the lower boundary of 16b1 were defined as the cranial and caudal border of para aortic CTV, respectively. For the study cohort, the mean distance from the volume center of all lymph nodes in 16a2 and 16b1 to the proximal border of the aorta was 9 mm (range 4-24) in the front, 7 mm (range 3-14) on the left, and 12 mm (range 5-29) on the right. For the validation cohort (n=19 patients, 56 PALN), the mean distance from the center of the lymph node to the border of the aorta were both 10 mm on the left (range 5-20) and right (range 6-23). The mean distance in front of the aorta was 9 mm (range 5–23). Finally, a CTV expansion from the aorta of 18 mm in the front, 12 mm on the left, and 24 mm on the right resulted in 96% (73/76) coverage of PALNs in the study cohort. At the time of the validation, the described CTV could include 96% (47/49) of recurrent PALNs in the validation cohort.ConclusionsThe involvement rates of PALNs in 16a2 and 16b1 were the highest. Based on the distribution of PALNs, a new para-aortic CTV was defined to construct a more accurate target volume for adjuvant radiotherapy in BTC.

Despite the fact that the water temperature of the Yangtze River has changed substantially due to the construction of Three Gorges Reservoir (TGR), little is known about how the thermal structure of TGR responded to the implementation of two large upstream reservoirs in 2013. We investigated the seasonal variations of water temperature and discharge in the middle reaches of the Yangtze River by analyzing multi-year (2004–2018) hydrological and water temperature data. The effects of upstream dams on the thermal regime, density currents and phytoplankton blooms in TGR were examined. The results show that water temperature in TGR increased in spring (+1.1 °C) and winter (+0.8 °C) seasons after the filling of upstream reservoirs compared to the years before. Longer duration of stratification is associated with a smaller discharge and a longer water residence time. Moreover, the increase of inflow, which was at least partially due to upstream dam construction, lead to the weakening of stratification during the spring season. As a consequence of the higher water temperature in TGR in spring, the density-driven exchange flows between the main reservoir and tributary bays have changed. Overflows became more frequent, which promoted the deepening of the surface mixing layer, and resulted in a dramatic reduction in the frequency and biomass of phytoplankton blooms in tributary bays of TGR.