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Abstract Background Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. Methods We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. Results The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p

Abstract Backgroud New-onset atrial fibrillation (NOAF) is a common complication of sepsis and linked to higher death rates in affected patients. The lack of effective predictive tools hampers early risk assessment for the development of NOAF. This study aims to develop practical and effective predictive tools for identifying the risk of NOAF. Methods This case-control study retrospectively analyzed patients with sepsis admitted to the emergency department of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from September 2017 to January 2023. Based on electrocardiographic reports and electrocardiogram monitoring records, patients were categorized into NOAF and non-NOAF groups. Laboratory tests, including myeloperoxidase (MPO) and hypochlorous acid (HOCl), were collected, along with demographic data and comorbidities. Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were employed to identify predictors. The area under the curve (AUC) was used to evaluate the predictive model’s performance in identifying NOAF. Results A total of 389 patients with sepsis were included in the study, of which 63 developed NOAF. MPO and HOCl levels were significantly higher in the NOAF group compared to the non-NOAF group. Multivariate logistic regression analysis identified MPO, HOCl, tumor necrosis factor-α (TNF-α), white blood cells (WBC), and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score as independent risk factors for NOAF in sepsis. Additionally, a nomogram model developed using these independent risk factors achieved an AUC of 0.897. Conclusion The combination of MPO and its derivative HOCl with clinical indicators improves the prediction of NOAF in sepsis. The nomogram model can serve as a practical predictive tool for the early identification of NOAF in patients with sepsis.

Abstract Superficial weathering in the form of granular disaggregation, powdering and flaking on stone surface is one of the most serious damages to stone heritages, since the surface carries most of the artistic, historical information. The determination of the thickness of the superficially weathered layer of historical stones is critical to their conservation. However, the methodology for quantitative analyses of such thickness remains very limited. In this study, we carefully study the vapor absorption and pore structure evolution of historical sandstones from Guanzhong area with respect to their weathering. We find out that the thickness of superficial weathered layer of Guanzhong sandstones can be derived by following the changes in vapor absorption or pore structure. Such data achieved from various methods developed in this work are consistent with each other and in good agreement with the results obtained by using current techniques such as drilling resistance measurement, the Ruxton method and ultrasonic testing. Among all methods used, pore size distribution analysis requires less sample preparation and measures the thickness of superficial weathered layer of Guanzhong sandstones around 7 mm.

Abstract Background Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) targeting the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c-Kit. This phase II study aimed to assess the efficacy and safety of anlotinib, either alone or in combination with bevacizumab (Bev) for recurrent high-grade glioma (rHGG) (NCT04822805, 30/03/2021). Methods Eligible patients had a histological diagnosis of rHGG with first or subsequent recurrences. All patients received oral anlotinib 12 mg or 10 mg on days 1–14 (repeated every 21 days). In cases where brain magnetic resonance imaging examination revealed an increase in peritumoral edema without worsening of symptoms, patients received a temporary treatment of intravenous bevacizumab 10 mg/kg to alleviate edema. The primary endpoint was the median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and safety. Results Twenty-five patients with rHGG were included in the efficacy and safety assessments. Eighteen patients received anlotinib alone, and seven patients received anlotinib in combination with Bev. For all patients, the mPFS and mOS were 5.0 months and 13.6 months, respectively. The ORR was 32%, and the DCR was 96%. It is noteworthy that the survival and response data of recurrent glioblastoma (rGBM) exhibit similarities to those of rHGG. For rGBM patients, there were no significant differences in mPFS, mOS, ORR, or DCR between the anlotinib alone and anlotinib + Bev groups. However, the incidence of treatment-related adverse events of any grade was higher in the anlotinib + Bev group compared to the anlotinib alone group (100% vs. 78%, p = 0.041). Conclusions Both anlotinib alone and its combination with Bev demonstrated good efficacy and safety in the treatment of rHGG.

Sharding is a critical technology for enhancing blockchain scalability. However, existing sharding blockchain protocols suffer from a high cross-shard ratio, high transaction latency, limited throughput enhancement, and high account migration. To address these problems, this paper proposes a sharding blockchain protocol for enhanced scalability and performance optimization through account transaction reconfiguration. Firstly, we construct a blockchain transaction account graph network structure to analyze transaction account correlations. Secondly, a modularity-based account transaction reconfiguration algorithm and a detailed account reconfiguration process is designed to minimize cross-shard transactions. Finally, we introduce a transaction processing mechanism for account transaction reconfiguration in parallel with block consensus uploading, which reduces the reconfiguration time overhead and system latency. Experimental results demonstrate substantial performance improvements compared to existing shard protocols: up to a 34.7% reduction in cross-shard transaction ratio, at least an 83.2% decrease in transaction latency, at least a 52.7% increase in throughput and a 7.8% decrease in account migration number. The proposed protocol significantly enhances the overall performance and scalability of blockchain, providing robust support for blockchain applications in various fields such as financial services, supply chain management, and industrial Internet of Things. It also enables better support for high-concurrency scenarios and large-scale network environments.

Spinal cord injury (SCI) can cause loss of sensory and motor function below the level of injury, posing a serious threat to human health and quality of life. One significant characteristic feature of pathological changes following injury in the nervous system is demyelination, which partially contributes to the long-term deficits in neural function after injury. The remyelination in the central nervous system (CNS) is mainly mediated by oligodendrocyte progenitor cells (OPCs). Numerous complex intracellular signaling and transcriptional factors regulate the differentiation process from OPCs to mature oligodendrocytes (OLs) and myelination. Studies have shown the importance of microRNA (miRNA) in regulating OPC functions. In this review, we focus on the demyelination and remyelination after SCI, and summarize the progress of miRNAs on OPC functions and remyelination, which might provide a potential therapeutic target for SCI treatments.

Abstract Background Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). Methods Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. Results Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. Conclusion Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Abstract Glycans, either alone or in complex with glycan-binding proteins, are essential structures that can regulate cell biology by mediating protein stability or receptor dimerization under physiological and pathological conditions. Certain glycans are ligands for lectins, which are carbohydrate-specific receptors. Bone is a complex tissue that provides mechanical support for muscles and joints, and the regulation of bone mass in mammals is governed by complex interplay between bone-forming cells, called osteoblasts, and bone-resorbing cells, called osteoclasts. Bone erosion occurs when bone resorption notably exceeds bone formation. Osteoclasts may be activated during cancer, leading to a range of symptoms, including bone pain, fracture, and spinal cord compression. Our understanding of the role of protein glycosylation in cells and tissues involved in osteoclastogenesis suggests that glycosylation-based treatments can be used in the management of diseases. The aims of this review are to clarify the process of bone resorption and investigate the signaling pathways mediated by glycosylation and their roles in osteoclast biology. Moreover, we aim to outline how the lessons learned about these approaches are paving the way for future glycobiology-focused therapeutics.

BackgroundOur center proposes a new technique that effectively provides space to broaden the surgical field of view and overcomes the limitations of endoscopy-assisted nipple-sparing mastectomy (E-NSM) by changing the dissection sequence and combining it with air inflation. The purpose of this study was to compare the clinical outcomes of the new technique designated “reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) with subpectoral breast reconstruction (SBR)“ and the conventional E-NSM (C-E-NSM) with SBR.MethodAll patients undergoing E-NSM with SBR at our breast center between April 2017 and December 2022 were included in this study. The cohort was divided into the C-E-NSM group and the R-E-NSM group. The operation time, anesthesia time, medical cost, complications, cosmetic outcomes, and oncological safety were compared.ResultsTwenty-six and seventy-nine consecutive patients were included in the C-E-NSM and R-E-NSM groups, with average ages of 36.9 ± 7.0 years and 39.7 ± 8.4 years (P=0.128). Patients in the R-E-NSM group had significantly shorter operation time (204.6 ± 59.2 vs. 318.9 ± 75.5 minutes, p

“Boundarics in Biomedicine” is a cutting-edge interdisciplinary discipline, which is of great significance for understanding the origin of life, the interaction between internal and external environments, and the mechanism of disease occurrence and evolution. Here, the definition of Boundarics in Biomedicine is first described, including its connotation, research object, research method, challenges, and future perspectives. “Boundarics in Biomedicine” is a cutting-edge interdisciplinary discipline involving multiple fields (e.g., bioscience, medicine, chemistry, materials science, and information science) dedicated to investigating and solving key scientific questions in the formation, identification, and evolution of living organism boundaries. Specifically, it encompasses 3 levels: (a) the boundary between the living organism and the external environment, (b) internal boundary within living organism, and (c) the boundary related to disease in living organism. The advancement of research in Boundarics in Biomedicine is of great scientific significance for understanding the origin of life, the interaction between internal and external environments, and the mechanism of disease occurrence and evolution, thus providing novel principles, technologies, and methods for early diagnosis and prevention of major diseases, personalized drug development, and prognosis assessment (Fig. 1).

Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1α. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.

Indoor PM2.5 pollution is one of the leading causes of death and disease worldwide. As monitoring indoor PM2.5 concentrations on a large scale is challenging, it is urgent to assess population-level exposure and related health risks to develop an easy-to-use and generalized model to predict indoor PM2.5 concentrations and spatiotemporal variations at the global level. Existing machine learning models of indoor PM2.5 are prone to deliver single-point predictions, and their input strategies are not widely applicable. Here, we developed a Bayesian neural network (BNN) model for predicting the distribution of daily average urban residential PM2.5 concentration based on multiple data sources available from nationwide comprehensive sensor-monitoring records in China. The BNN model showed good performance with a 10-fold cross-validation R2 of 0.70, mean-absolute-error of 9.45 μg/m3, root-mean-square error of 13.3 μg/m3, and 95 % prediction interval coverage of 85 %. To demonstrate the application process, this model was applied to predict indoor PM2.5 concentrations on a large spatiotemporal scale. Our modeled population-weighted annual indoor PM2.5 concentration for China in 2019 was 22.8 μg/m3, far exceeding the WHO standard. The validity of the model at the population level can be further bolstered, making it valuable for assessing and managing indoor air pollution-related health risks.

Background Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological toxicities. More effective therapeutic strategies are urgently needed.Methods Primary triple negative breast cancer tumors were stained for cytosolic single-stranded DNA (ssDNA) using multiplex immunohistochemical staining. To increase cytosolic ssDNA, we genetically silenced TREX1. The role of tumor cytosolic ssDNA in promoting tumor immunogenicity and antitumor immune response was evaluated using murine breast cancer models.Results We found the tumorous cytosolic ssDNA is associated with tumor-infiltrating lymphocyte in patients with triple negative breast cancer. TREX1 deficiency triggered a STING-independent innate immune response via DDX3X. Cytosolic ssDNA accumulation in tumors due to TREX1 deletion is sufficient to drastically improve the efficacy of ICB. We further identified a cytosolic ssDNA inducer CEP-701, which sensitized breast tumors to ICB without the toxicities associated with inhibiting DNA damage response.Conclusions This work demonstrated that cytosolic ssDNA accumulation promotes breast cancer immunogenicity and may be a novel therapeutic strategy to improve the efficacy of ICB with minimal toxicities.

Nitrogen (N) deposition rates of terrestrial ecosystems have gradually declined but are still high in some areas. Previous studies have reported that N addition elicits diverse impacts on soil organic carbon (SOC) pools. SOC can be divided into different functional fractions, namely, particulate organic carbon (POC) and mineral-associated organic carbon (MAOC). The responses of these fractions to N addition should be elucidated to better understand the changes in SOC pools. Here, we conducted a N addition experiment (0, 40, and 80 kg N ha−1 yr−1) in a subtropical Castanopsis fabri forest to simulate N deposition. The surface (0−10 cm) SOC fractions, aboveground litter product, fine root (diameter < 2 mm) biomass, soil exchangeable cation content, and soil enzyme activity under different N addition treatments were measured. The results showed the following: (1) N addition showed a positive effect on POC and SOC contents but did not significantly affect MAOC content; (2) POC content was negatively correlated with pH and soil enzyme activity and positively correlated with aboveground litter product, suggesting that POC accumulation was influenced by aboveground litter input and microbial decomposition; (3) a close negative relationship was observed between exchangeable Al3+ and Ca2+ or K+ contents, indicating that there is likely to be a trade-off between the mineral sorption and desorption, thus resulting in an insignificant reaction of MAOC to N addition. Overall, the accumulation of SOC under short-term N addition was found to be primarily driven by POC, and the response of different SOC functional fractions to N addition was inconsistent. By incorporating these nuances into ecosystem models, it is possible to predict SOC dynamics more accurately in response to global change.

Purpose To analyse the clinical symptoms, laboratory examinations and chest CT findings of children infected by the B.1.617.2 variant of COVID-19 and to compare the differences between clinical subtypes.Methods Fifty-three children (28 males, 25 females; age ranging from 4 months to 17 years) were included with B.1.617.2 variant infection in Nanjing, China, from July 21 to August 12 2021. Clinical data from patients were collected and analysed in groups of mild and common types. Imaging data were divided into three stages for evaluation: early, intermediate and late stages.Results In our study, fever (53%), cough (34%) and pharyngeal discomfort (28%) were the main symptoms. There were no differences in clinical symptoms between the mild and common type. The most common laboratory test items outside the normal range were decreased mean corpuscular volume (68%), lymphocyte percentage (64% elevated and 2% decreased) and decreased serum alkaline phosphatase concentration (66%). The differences in haemoglobin and monocyte percentages between the mild and common types were statistically significant (p = .037 and .033, respectively). No influencing factor was statistically significant in the regression analysis of both symptoms and clinical subtypes. The main CT findings were ground-glass opacity and consolidation located in the periphery and bilateral multilobed involvement. The mean CT score was 1.6. CT score correlated with packet cell volume, haemoglobin, mean erythrocyte volume, mean platelet volume and platelet distribution width.Conclusion The pathogenetic condition of children with B.1.617.2 variant infection is mild. Although there were intergroup differences in some blood cell analyses, T-lymphocyte counts, and comprehensive biochemical indicators, no factors had a significant effect on clinical typing and the presence or absence of symptoms. CT findings and CT scores reflect disease stage and pathological changes and correlate moderately with laboratory tests, making them of good value for disease diagnosis and monitoring.Key MessagesPaediatric patients infected with B.1.617.2 variant have a milder clinical and imaging presentation than adults and are similar to the prototype infection.CT findings and scores which reflect disease stages and pathological changes.There is a correlation between chest CT and laboratory tests, which can be useful for the diagnosis and follow-up of the disease.

Abstract Although the SARS-CoV-2 vaccine has been widely used worldwide, not all individuals can produce neutralization antibodies, so it is still urgent to find and prepare neutralization antibodies for COVID-19 prevention or treatment. In this study, we created a new strategy to effectively obtain neutralizing antibodies or complementary determining region 3 (CDR3) of neutralizing antibodies against SARS-CoV-2. We first predicted and synthesized several B cell epitopes on RBD and adjacent RBD of S protein, then the B cell epitopes were used to prepare affinity chromatography columns respectively and purify the binding IgG from serum samples of convalescent COVID-19 patients. After these IgGs were identified to have neutralizing activity, the peptide sequences of the antigen-binding regions (variable region) of neutralizing antibodies were analyzed by protein mass spectrometry. Subsequently, the B cells from the same individual were sorted and used to obtain their full BCR repertoire by 5′ RACE combined with high-throughput of PacBio sequencing method. Then, the peptide sequence of neutralizing antibody variable region by protein mass spectrometry was mapped to the full BCR repertoire and found the full variable region sequence of neutralizing antibodies. Finally, we obtained and synthesized numerous CDR3 peptides of neutralizing antibodies to confirm the neutralizing activity for SARS-CoV-2 infection. Our results indicate that the novel scheme will be suitable for rapid screening of neutralizing antibodies, including screening neutralizing antibodies against SARS-CoV-2 and other pathogenic microorganisms.

The increase in carbon dioxide emissions has significantly impacted human society and the global environment. As carbon dioxide is the most abundant and cheap C1 resource, the conversion and utilization of carbon dioxide have received extensive attention from researchers. Among the many carbon dioxide conversion and utilization methods, the reverse water–gas conversion (RWGS) reaction is considered one of the most effective. This review discusses the research progress made in RWGS with various heterogeneous metal catalyst types, covering topics such as catalyst performance, thermodynamic analysis, kinetics and reaction mechanisms, and catalyst design and preparation, and suggests future research on RWGS heterogeneous catalysts.

Voltage-gated sodium channels located in axon initial segments (AIS) trigger action potentials (AP) and play pivotal roles in the excitability of cortical pyramidal neurons. The differential electrophysiological properties and distributions of NaV1.2 and NaV1.6 channels lead to distinct contributions to AP initiation and propagation. While NaV1.6 at the distal AIS promotes AP initiation and forward propagation, NaV1.2 at the proximal AIS promotes the backpropagation of APs to the soma. Here, we show the small ubiquitin-like modifier (SUMO) pathway modulates Na+ channels at the AIS to increase neuronal gain and the speed of backpropagation. Since SUMO does not affect NaV1.6, these effects were attributed to SUMOylation of NaV1.2. Moreover, SUMO effects were absent in a mouse engineered to express NaV1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of NaV1.2 exclusively controls INaP generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.

Abstract Introduction Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer. Methods One hundred and thirteen patients with lung cancer and 99 age‐matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony‐stimulating factors were detected by enzyme‐linked immunosorbent assay (ELISA). Results A reduction in antitumor NK cells (p

ObjectivesIn recent years, the desire to make a more fine-grained identification on mild cognitive impairment (MCI) has become apparent, the etiological diagnosis of MCI in particular. Nevertheless, new methods for the etiological diagnosis of MCI are currently insufficient. The objective of this study was to establish discriminative measures for amnestic mild cognitive impairment (a-MCI) and MCI caused by cerebral small vessel disease (CSVD).Materials and methodsIn total, 20 normal controls (NCs), 33 a-MCI patients, and 25 CSVD-MCI patients performed comprehensive neuropsychological assessments concerning global cognitive function and five cognitive domains as well as magnetic resonance imaging scan with diffusion tensor imaging (DTI). Diffusion parameters including fractional anisotropy and mean diffusivity of 20 major white matter metrics were obtained by ROI-based analyses. The neuropsychological tests and diffusion measurements were compared and binary logistic regression was used to identify the best differential indicator for the two MCI subgroups. The discriminating power was calculated by receiver operating characteristic analysis.ResultsAmnestic mild cognitive impairment group showed significant impairment in memory and language function, while CSVD-MCI group revealed more deficits in multi-cognitive domains of memory, language, attention and executive function than controls. Compared to the a-MCI, CSVD-MCI was significantly dysfunctional in the executive function. The CSVD-MCI group had decreased fractional anisotropy and increased mean diffusivity values throughout widespread white matter areas. CSVD-MCI presented more severe damage in the anterior thalamic radiation, forceps major, forceps minor and right inferior longitudinal fasciculus compared with a-MCI group. No significant neuropsychological tests were found in the binary logistic regression model, yet the DTI markers showed a higher discriminative power than the neuropsychological tests. The Stroop test errors had moderate potential (AUC = 0.747; sensitivity = 76.0%; specificity = 63.6%; P = 0.001; 95% CI: 0.617–0.877), and the mean diffusivity value of forceps minor demonstrated the highest predictive power to discriminate each MCI subtype (AUC = 0.815; sensitivity = 88.0%; specificity = 72.7%; P < 0.001; 95% CI: 0.698–0.932).ConclusionThe mean diffusivity of forceps minor may serve as an optimal indicator to differentiate between a-MCI and CSVD-MCI.

Macronaria is a clade of gigantic body-sized sauropod dinosaurs widely distributed from the Late Jurassic to the Late Cretaceous globally. However, its origin, early diversification, and dispersal are still controversial. Here, we report a new macronarian Yuzhoulong qurenensis gen. et sp. nov. excavated from the Middle Jurassic (Bathonian) Lower Shaximiao Formation. Yuzhoulong qurenensis bears a unique combination of features, such as two accessory fossae that exist on the posterior surface of dorsal diapophyses of anterior dorsal vertebrae. Results of phylogenetic analyses demonstrate it is one of the earliest-diverging macronarians. This new material represents a Middle Jurassic fossil record of macronarian sauropod worldwide and improves the understanding of the early diversity and dispersal of the Neosauropoda. This discovery further supports that sauropods achieved a more rapid and varied morphological diversity and palaeogeographical dispersal in the Middle Jurassic.

Traditional Chinese medicine (TCM) usually acts in the form of compound prescriptions in the treatment of complex diseases. The herbs contained in each prescription have the dual nature of efficiency and toxicity due to their complex chemical component, and the principle of prescription is usually to increase efficiency and reduce toxicity. At present, the studies on prescriptions have mainly focused on the consideration of the material basis and possible mechanism of the action mode, but the quantitative research on the compatibility rule of increasing efficiency and reducing toxicity is still the tip of the iceberg. With the extensive application of computational pharmacology technology in the research of TCM prescriptions, it is possible to quantify the mechanism of synergism and toxicity reduction of the TCM formula. Currently, there are some classic drug pairs commonly used to treat complex diseases, such as Tripterygium wilfordii Hook. f. with Lysimachia christinae Hance for lung cancer, Aconitum carmichaelii Debeaux with Glycyrrhiza uralensis Fisch. in the treatment of coronary heart disease, but there is a lack of systematic quantitative analysis model and strategy to quantitatively study the compatibility rule and potential mechanism of synergism and toxicity reduction. To address this issue, we designed an integrated model which integrates matrix decomposition and shortest path propagation, taking into account both the crosstalk of the effective network and the propagation characteristics. With the integrated model strategy, we can quantitatively detect the possible mechanisms of synergism and attenuation of Tripterygium wilfordii Hook. f. and Lysimachia christinae Hance in the treatment of lung cancer. The results showed the compatibility of Tripterygium wilfordii Hook. f. and Lysimachia christinae Hance could increase the efficacy and decrease the toxicity of lung cancer treatment through MAPK pathway and PD-1 checkpoint pathway in lung cancer.

ObjectiveTo compare and evaluate radiomics models to preoperatively predict β-catenin mutation in patients with hepatocellular carcinoma (HCC).MethodsNinety-eight patients who underwent preoperative gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI were retrospectively included. Volumes of interest were manually delineated on arterial phase, portal venous phase, delay phase, and hepatobiliary phase (HBP) images. Radiomics features extracted from different combinations of imaging phases were analyzed and validated. A linear support vector classifier was applied to develop different models.ResultsAmong all 15 types of radiomics models, the model with the best performance was seen in the RHBP radiomics model. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity of the RHBP radiomics model in the training and validation cohorts were 0.86 (95% confidence interval [CI], 0.75–0.93), 0.75, 1.0, and 0.65 and 0.82 (95% CI, 0.63–0.93), 0.73, 0.67, and 0.76, respectively. The combined model integrated radiomics features in the RHBP radiomics model, and signatures in the clinical model did not improve further compared to the single HBP radiomics model with AUCs of 0.86 and 0.76. Good calibration for the best RHBP radiomics model was displayed in both cohorts; the decision curve showed that the net benefit could achieve 0.15. The most important radiomics features were low and high gray-level zone emphases based on gray-level size zone matrix with the same Shapley additive explanation values of 0.424.ConclusionThe RHBP radiomics model may be used as an effective model indicative of HCCs with β-catenin mutation preoperatively and thus could guide personalized medicine.

PurposeTo establish an ensemble machine learning (ML) model for predicting the risk of futile recanalization, malignant cerebral edema (MCE), and cerebral herniation (CH) in patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and recanalization.MethodsThis prospective study included 110 patients with premorbid mRS ≤ 2 who met the inclusion criteria. Futile recanalization was defined as a 90-day modified Rankin Scale score >2. Clinical and imaging data were used to construct five ML models that were fused into a logistic regression algorithm using the stacking method (LR-Stacking). We added the Shapley Additive Explanation method to display crucial factors and explain the decision process of models for each patient. Prediction performances were compared using area under the receiver operating characteristic curve (AUC), F1-score, and decision curve analysis (DCA).ResultsA total of 61 patients (55.5%) experienced futile recanalization, and 34 (30.9%) and 22 (20.0%) patients developed MCE and CH, respectively. In test set, the AUCs for the LR-Stacking model were 0.949, 0.885, and 0.904 for the three outcomes mentioned above. The F1-scores were 0.882, 0.895, and 0.909, respectively. The DCA showed that the LR-Stacking model provided more net benefits for predicting MCE and CH. The most important factors were the hypodensity volume and proportion in the corresponding vascular supply area.ConclusionUsing the ensemble ML model to analyze the clinical and imaging data of AIS patients with successful recanalization at admission and within 24 h after MT allowed for accurately predicting the risks of futile recanalization, MCE, and CH.

The human voltage-gated proton channel (hHv1) maintains intracellular pH and membrane potential in sperm and neutrophils. Here, the authors show that albumin activates hHv1, by binding to the channel voltage sensor domains to enhance open probability and increases proton current, and that activation is required to trigger sperm to allow oocyte fertilization and to sustain production and release of immune inflammatory mediators during the neutrophil respiratory burst.

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019 (COVID-19) who progressed from the nonsevere condition on admission to severe during hospitalization. This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10, 2020 to Feb 7, 2020. In the training cohort, independent risk factors associated with disease progression were identified by univariate and multivariate analyses. The prognostic nomogram was established and then validated externally using C-index. The study included 351 patients (293 and 58 in the training and validation cohorts, respectively), with 27 (9.2%) and 5 (8.6%) patients progressed, respectively. In the training cohort, older age (OR 1.036, 95% CI 1.000–1.073), more lobes involved on chest CT (OR 1.841, 95% CI 1.117–3.035), comorbidity present (OR 2.478, 95% CI 1.020–6.018), and lower lymphocyte count (OR 0.081, 95% CI 0.019–0.349) were identified as independent risk factors. The prognostic nomogram was established in the training cohort with satisfied external prognostic performance (C-index 0.906, 95% CI 0.806–1.000). In conclusion, older age, comorbidity present, more lobes involved on chest CT, and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.

FeCrAl is regarded as one of the most promising cladding materials for accident-tolerant fuel at nuclear fission reactors due to its comprehensive properties of inherent corrosion resistance, excellent irradiation resistance, high-temperature oxidation resistance, and stress corrosion cracking resistance. In this work, the irradiation response of FeCrAl irradiated by 2.4 MeV He2+ ions with a fluence of 1.1 × 1016 cm−2 at room temperature was studied using X-ray diffraction, transmission electron microscopy, and nanoindentation. The characterization results of structural and mechanical properties showed that only black-dot defects exist in irradiated FeCrAl samples, and that the hardness of the irradiated samples was 11.5% higher than that of the unirradiated samples. Similar to other types of radiation defects, black-dot defects acted as fixed defect obstacles and hindered the movement of slip dislocations moving under the applied load, resulting in a significant increase in the hardness of FeCrAl. Importantly, this work points out that irradiation-induced black-dot defects can significantly affect the mechanical properties of materials, and that their contribution to radiation hardening cannot be ignored.

Background: Antibodies induced by viral infection can not only prevent subsequent virus infection, but can also mediate pathological injury following infection. Therefore, understanding the B-cell receptor (BCR) repertoire of either specific neutralizing or pathological antibodies from patients convalescing from Coronavirus disease 2019 (COVID-19) infection is of benefit for the preparation of therapeutic or preventive antibodies, and may provide insight into the mechanisms of COVID-19 pathological injury. Methods: In this study, we used a molecular approach of combining 5’ Rapid Amplification of cDNA Ends (5’-RACE) with PacBio sequencing to analyze the BCR repertoire of all 5 IgH and 2 IgL genes in B-cells harvested from 35 convalescent patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: We observed numerous BCR clonotypes within most COVID-19 patients, but not in healthy controls, which validates the association of the disease with a prototypical immune response. In addition, many clonotypes were found to be frequently shared between different patients or different classes of antibodies. Conclusions: These convergent clonotypes provide a resource to identify potential therapeutic/prophylactic antibodies, or identify antibodies associated with pathological effects following infection with SARS-CoV-2.

Vaccination against COVID-19 is critical for immuno-compromised individuals, including patients with cancer. Systemic reactogenicity, a manifestation of the innate immune response to vaccines, occurs in up to 69% of patients following vaccination with RNA-based COVID-19 vaccines. Tumor regression can occur following an intense immune-inflammatory response and novel strategies to treat cancer rely on manipulating the host immune system. Here, we report spontaneous regression of metastatic salivary gland myoepithelial carcinoma in a patient who experienced grade 3 systemic reactogenicity, following vaccination with the mRNA-1273 COVID-19 vaccine. Histological and immunophenotypic inspection of the postvaccination lung biopsy specimens showed a massive inflammatory infiltrate with scant embedded tumor clusters (

Background. Of all intestinal microbiome-derived metabolites, trimethylamine N-oxide (TMAO) has received increasing attention because of its potent role in colorectal cancer development. Accumulating evidence suggests that TMAO generated by the gut microbiota is a new and important player in the etiological process of colorectal cancer. Nevertheless, the carcinogenic mechanism of TMAO in colorectal cancer remains unclear. In this study, TMAO induced colorectal cancer cell proliferation and produced higher vascular endothelial growth factor A (VEGFA) levels in vitro. In vivo, after long-term choline feeding in tumor-bearing mice, circulating TMAO levels, tumor volume, new blood vessel formation, and VEGFA and CD31 amounts were increased significantly. This study revealed that TMAO exerts oncogenic effects by promoting cell proliferation and angiogenesis in colorectal cancer.

Objective: The study was aimed to describe the clinical characteristics and evaluate the dynamic changes of chest CT features in the first three weeks in the common type fo COVID-19 pneumonia patients in Jiangsu Province. Methods: 307 patients infected SARS-CoV-2 classified as common type were enrolled in the study. 628 chest CT scans were divided into three groups based on the time interval between symptoms and chest CT scan. The clinical characteristics were descriptively analyzed.The chest CT features were quantitatively evaluated. Mann-Whitney U test was used to test the differences in three groups and between men and women. Spearman rank correlation was used to test the association between the arterial blood gas(ABG) analysis results and chest CT scores. Results: Fever (69.1%) and cough (62.8%) were common symptoms. 111(36.2%) patients were anorexia. GGO was the most common manifestation of COVID-19 pneumonia, which could be followed by consolidation and fibrosis. Lower lobe or subpleural region was the most common distribution form of lesion. More lung lobes were involved in the third week. Total chest CT scores in the second week were higher than the first week. Fibrosis Scores increased in the second and third week. Total CT score, GGO score and fibrosis score of male patients were significantly higher than female in the second week. Male patients had higher consolidation score and fibrosis score than female in the third week. Total CT score and GGO score had weak to moderate correlation with arterial blood gas indices. Conclusion: Changes in chest CT were difficult to assess quantitatively in the first third weeks. Male patients recovered slower than female in the second week. Although CT score had correlations with arterial blood gas indices, long-term follow-up of pulmonary function test is needed to determine the recovery of lung.

Background: A pneumonia associated with the coronavirus disease 2019 (COVID-19) recently emerged in China. It was recognized as a global health hazard. Methods: 234 inpatients with COVID-19 were included. Detailed clinical data, chest HRCT basic performances and certain signs were recorded Ground-glass opacity (GGO), consolidation, fibrosis and air trapping were quantified. Both clinical types and CT stages were evaluated. Results: Most patients (approximately 90%) were classified as common type and with epidemiologic history. Fever and cough were main symptoms. Chest CT showed abnormal attenuation in bilateral multiple lung lobes, distributed in the lower and/or periphery of the lungs (94.98%), with multiple shapes. GGO and vascular enhancement sign were most frequent seen, followed by interlobular septal thickening and air bronchus sign as well as consolidation, fibrosis and air trapping. There were significant differences in most of CT signs between different stage groups. The SpO2 and OI were decreased in stage IV, and the CT score of consolidation, fibrosis and air trapping was significantly lower in stage I (P

Abstract Background To explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) to identify the differentiated degree of hepatocellular carcinoma (HCC). Method One hundred four participants were enrolled in this retrospective study. Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture features were analyzed by MaZda, and B11 program was used for data analysis and classification. The diagnosis efficiencies of texture features and conventional imaging features in identifying the differentiated degree of HCC were assessed by receiver operating characteristic analysis. The relationship between texture features and differentiated degree of HCC was evaluated by Spearman’s correlation coefficient. Results The grey-level co-occurrence matrix -based texture features were most frequently extracted and the nonlinear discriminant analysis was excellent with the misclassification rate ranging from 3.33 to 14.93%. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively, while the AUC of tumor size was 0.649, 0.660 and 0.517 respectively. The tumor size was significantly different between poorly- and moderately-HCC (p = 0.014). The COMBINE AUC values were not increased with tumor size combined. Conclusions Texture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI was valuable and might be a promising method in identifying the differentiated degree of HCC. The poorly-differentiated HCC was more heterogeneous than well- and moderately-differentiated HCC.

In a cyber-physical power system, active distribution network (ADN) facilitates the energy control through hierarchical and distributed control system (HDCS). Various researches have dedicated to develop the control strategies of primary devices of ADN. However, an ADN demonstration project shows that the information transmission of HDCS may cause time delay and response lag, and little model can describe both the ADN primary device and HDCS as a cyber-physical system (CPS). In this paper, a hybrid system based CPS model is proposed to describe ADN primary devices, control information flow, and HDCS. Using the CPS model, the energy process of primary devices and the information process of HDCS are optimized by model predictive control (MPC) methodology to seamlessly integrate the energy flow and the information flow. The case study demonstrates that the proposed CPS model can accurately reflect main features of HDCS, and the control technique can effectively achieve the operation targets on primary devices despite the fact that HDCS brings adverse effects to control process.

PICALM rs3851179, one of the genes most frequently linked to susceptibility of late-onset Alzheimer’s disease (LOAD), plays a crucial role in regulating amyloid precursor protein, and amyloid β (Aβ) transcytosis. To explore the effects of PICALM and AD continuum stage on cortex thickness, CSF Aβ, and tau, 188 cognitively normal controls, 261 MCI patients, and 140 early LOAD patients were recruited, and each group was divided into rs3851179 A-carriers and GG-carriers. A full factorial ANCOVA was used to analyze the main effects and interactive effects of AD continuum stage, and PICALM. The interactive effects of AD continuum stage and PICALM on cortex thickness and CSF biomarkers were not significant. The main effect of PICALM was significant on the left postcentral cortex thickness, and the cortex thickness of A-carriers was less than that of GG-carriers. The rs3851179 A-carriers displayed higher Aβ42 levels and Aβ42/40 ratios, and lower P/T–tau ratios, compared with GG-carriers. A higher MMSE score was found in A-carriers among the LOAD patients. In conclusion, the main effects of PICALM were independent of AD continuum stage, and PICLAM rs3851179 genotypes may modulate left postcentral cortex thickness, Aβ42 level, and P/T–tau ratio. The rs3851179 A-allele may protect the cognitive function of LOAD patients.

Due to the fragile physicochemical properties of hazardous chemicals, the chances of leakage and explosion during production, transportation, and storage are quite high. In recent years, hazardous chemical accidents have occurred frequently, posing a great threat to people’s lives and property. Hence, it is crucial to analyze hazardous chemical accidents and establish corresponding warning mechanisms and safeguard measures. At present, most hazardous-chemical-accident data exist in text format. However, named entity recognition (NER), as a method to extract useful information from text data, has not been fully utilized in the field of Chinese hazardous-chemical handling. The challenge is that Chinese NER is more difficult than English NER, because the boundaries of Chinese are fuzzy. In addition, the descriptions of hazardous chemical accidents are colloquial and lacks relevant labeling data. Further, most current models do not consider identifying the entities related to accident scenarios, losses, and causes. To tackle these issues, we propose a model based on a rule template and Bert-BiLSTM-CRF (RT-BBC) to recognize named entities from unstructured Chinese hazardous chemical accident reports. Comprehensive experiments on real-world datasets show the effectiveness of the proposed method. Specifically, RT-BBC outperformed the most competitive method by 6.6% and 3.6% in terms of accuracy and F1.

The disc-milling method is expected to increase the grooving efficiency of blisks. However, there are few studies about the residual stress on a blisk during disc-milling grooving. In this study, a single-factor experiment and an orthogonal experiment of blisk disc-milling and grooving were designed to obtain the residual stress. Surface subsurface residual stress were also studied. The results showed that the surface of the milling groove bore compressive stress. Residual stress decreased with increasing spindle speed and increased with increasing feed speed and spindle rotation angle. Moreover, residual stress was most sensitive to spindle rotation angle and least sensitive to feed speed. A higher residual stress produced on the machined surface led to a deeper layer of residual stress.

BackgroundImmunotherapy, adjuvant chemotherapy, and prognosis of colorectal cancer are associated with MSI. Biopsy pathology cannot fully reflect the MSI status and heterogeneity of rectal cancer.PurposeTo develop a radiomic-based model to preoperatively predict MSI status in rectal cancer on MRI.AssessmentThe patients were divided into two cohorts (training and testing) at a 7:3 ratio. Radiomics features, including intensity, texture, and shape, were extracted from the segmented volumes of interest based on T2-weighted and ADC imaging.Statistical TestsIndependent sample t test, Mann-Whitney test, the chi-squared test, Receiver operating characteristic curves, calibration curves, decision curve analysis and multi-variate logistic regression analysisResultsThe radiomics models were significantly associated with MSI status. The T2-based model showed an area under the curve of 0.870 with 95% CI: 0.794–0.945 (accuracy, 0.845; specificity, 0.714; sensitivity, 0.976) in training set and 0.895 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.887; sensitivity, 0.772) in testing set. The ADC-based model had an AUC of 0.790 with 95% CI: 0.794–0.945 (accuracy, 0.774; specificity, 0.714; sensitivity, 0.976) in training set and 0.796 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.889; sensitivity, 0.772) in testing set. The combined model integrating T2 and ADC features showed an AUC of 0.908 with 95% CI: 0.845–0.971 (accuracy, 0.857; specificity, 0.762; sensitivity, 0.952) in training set and 0.926 with 95% CI: 0.813-1.000 (accuracy, 0.852; specificity, 1.000; sensitivity, 0.778) in testing set. Calibration curve showed that the combined score had a good calibration degree, and the decision curve demonstrated that the combined score was of benefit for clinical use.Data ConclusionRadiomics analysis of T2W and ADC images showed significant relevance in the prediction of microsatellite status, and the accuracy of combined model of ADC and T2W features was better than either alone.

Circular RNA (circRNA) is often regarded as a special kind of non-coding RNA, involved in the regulation mechanism of various diseases, such as tumors, neurological diseases, and inflammation. In a broad spectrum of biological processes, the modification of the 76-amino acid ubiquitin protein generates a large number of signals with different cellular results. Each modification may change the result of signal transduction and participate in the occurrence and development of diseases. Studies have found that circRNA-mediated ubiquitination plays an important role in a variety of diseases. This review first introduces the characteristics of circRNA and ubiquitination and summarizes the mechanism of circRNA in the regulation of ubiquitination in various diseases. It is hoped that the emergence of circRNA-mediated ubiquitination can broaden the diagnosis and prognosis of the disease.

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome, similar to other chronic pains, the mechanisms of which are not fully understood. To further understand the neural mechanism of this chronic pain and its transition, we performed functional magnetic resonance imaging (fMRI) scans on PHN rat models. Twelve PHN rat models were established by intraperitoneal injection of resiniferatoxin, with an additional 12 rats serving as controls. Nociceptive behavioral tests were performed on these rats and fMRI scans were performed on days 7 and 14 after modeling. Functional connection (FC) analysis was used to investigate the brain FC alterations associated with chronic pain in PHN rats, with the anterior cingulate cortex (ACC) as a seed. Nociceptive behavioral tests showed that PHN rats presented symptoms similar to those of PHN patients. FC analysis showed that compared to the control group, the PHN group showed different FC patterns on days 7 and 14. As can be seen, the brain FC alterations in the rat model of PHN changed dynamically, shifting from brain regions processing sensory information to regions processing emotions and motives.

Previous studies have revealed highly reproducible patterns of temporally lagged brain activity in healthy human adults. However, it is unknown whether temporal organization of intrinsic activity is altered in migraines or if it relates to migraine chronification. In this resting-state functional magnetic resonance imaging study, temporal features of intrinsic activity were investigated using resting-state lag analysis, and 39 episodic migraine patients, 17 chronic migraine patients, and 35 healthy controls were assessed. Temporally earlier intrinsic activity in the hippocampal complex was revealed in the chronic migraine group relative to the other two groups. We also found earlier intrinsic activity in the medial prefrontal cortex in chronic compared with episodic migraines. Both migraine groups showed earlier intrinsic activity in the lateral temporal cortex and sensorimotor cortex compared with the healthy control group. Across all patients, headache frequency negatively correlated with temporal lag of the medial prefrontal cortex and hippocampal complex. Disrupted propagation of intrinsic activity in regions involved in sensory, cognitive and affective processing of pain may contribute to abnormal brain function during migraines. Decreased time latency in the lateral temporal cortex and sensorimotor cortex may be common manifestations in episodic and chronic migraines. The temporal features of the medial prefrontal cortex and hippocampal complex were associated with migraine chronification.

BackgroundPigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy.MethodIn this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14+ cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function.ResultsThe most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA.ConclusionThe transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.

The p38 regulated/activated protein kinase (PRAK) is a protein kinase downstream of p38MAPK. The present study investigated its function in the macrophage. Myeloid-specific deletion of Prak resulted in a significant reduction in F4/80+CD11b+ peritoneal macrophages with decreased expression of MHC-II and CD80. Upon infection with Listeria monocytogenes, Prak-deficient mice demonstrated an increased mortality, which was accompanied by a higher bacterial load in multiple tissues and elevated levels of proinflammatory cytokines in the serum. While the Prak-deficient macrophage showed similar potency in phagocytosis assays, its bactericidal activity was severely impaired. Moreover, Prak deficiency was associated with defects in ROS production, inflammasome activation as well as autophagy induction. Therefore, PRAK critically contributes to the clearance of intracellular pathogens by affecting multiple aspects of the macrophage function.

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

To explore the evaluation of white matter structural network analysis in the differentiation of Alzheimer’s disease (AD) and subcortical ischemic vascular dementia (SIVD), 67 participants [31 AD patients, 19 SIVD patients, and 19 normal control (NC)] were enrolled in this study. Each participant underwent 3.0T MRI scanning. Diffusion tensor imaging (DTI) data were analyzed by graph theory (GRETNA toolbox). Statistical analyses of global parameters [gamma, sigma, lambda, global shortest path length (Lp), global efficiency (Eg), and local efficiency (Eloc)] and nodal parameters [betweenness centrality (BC)] were obtained. Network-based statistical analysis (NBS) was employed to analyze the group differences of structural connections. The diagnosis efficiency of nodal BC in identifying different types of dementia was assessed by receiver operating characteristic (ROC) analysis. There were no significant differences of gender and years of education among the groups. There were no significant differences of sigma and gamma in AD vs. NC and SIVD vs. NC, whereas the Eg values of AD and SIVD were statistically decreased, and the lambda values were increased. The BC of the frontal cortex, left superior parietal gyrus, and left precuneus in AD patients were obviously reduced, while the BC of the prefrontal and subcortical regions were decreased in SIVD patients, compared with NC. SIVD patients had decreased structural connections in the frontal, prefrontal, and subcortical regions, while AD patients had decreased structural connections in the temporal and occipital regions and increased structural connections in the frontal and prefrontal regions. The highest area under curve (AUC) of BC was 0.946 in the right putamen for AD vs. SIVD. White matter structural network analysis may be a potential and promising method, and the topological changes of the network, especially the BC change in the right putamen, were valuable in differentiating AD and SIVD patients.

Background: Hypothesis-driven functional connectivity (FC) analyses have revealed abnormal functional interaction of regions or networks involved in pain processing in episodic migraine patients. We aimed to investigate the resting-state FC patterns in episodic migraine by combining data-driven voxel-wise degree centrality (DC) calculation and seed-based FC analysis.Methods: Thirty-nine patients suffering from episodic migraine without aura and 35 healthy controls underwent clinical assessment and functional MRI. DC was analyzed voxel-wise and compared between groups, and FC of regions with DC differences were further examined using a seed-based approach.Results: Compared with the control group, the migraine group showed increased and decreased DC in the right posterior insula and left crus I, respectively. Seed-based FC analyses revealed that migraine patients demonstrated increased right posterior insula connections with the postcentral gyrus, supplementary motor area/paracentral lobule, fusiform gyrus and temporal pole. The left crus I showed decreased FC with regions of the default mode network (DMN), including the medial prefrontal cortex (mPFC), angular gyrus, medial and lateral temporal cortex in patients with migraine. Furthermore, pain intensity positively correlated with DC in the right amygdala/parahippocampal gyrus, and migraine frequency negatively correlated with FC between the left crus I and mPFC.Conclusion: Patients with episodic migraine without aura have increased FC with the right posterior insula and decreased FC within the DMN, which may underlie disturbed sensory integration and cognitive processing of pain. The left crus I-mPFC connectivity may be a useful biomarker for assessing migraine frequency.