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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.

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.

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.

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.

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.

The FeCrAl alloy system is recognized as one of the candidate materials for accident-tolerant fuel (ATF) cladding in the nuclear power industry due to its high oxidation resistance under irradiation and high-temperature environments. The concentrations of Cr and Al have a significant effect on elastic properties of the FeCrAl alloy. In this work, elastic constants C11, C12, C44, bulk modulus and shear modulus of FeCrAl alloy were calculated with molecular dynamics methods. We explored compositions with 1–15 wt.% Cr and 1–5 wt.% Al at temperatures from 0 K to 750 K. The results show that the concentrations of Al and Cr have different effects on the elastic constants. When the concentration of Al was fixed, a decrease in bulk modulus and shear modulus with increasing Cr content was observed, consistent with previous experimental results. The dependence of elastic constants on temperature was also the same as in the experiments. Investigations into elastic properties of defect-containing alloys have shown that vacancies, voids, interstitials and Cr-rich precipitations have different effects on elastic properties of FeCrAl alloys. Investigations of elastic properties of defect-containing alloys have shown that vacancies, void, interstitials and Cr-rich precipitations have different effects on elastic properties of FeCrAl alloys. Therefore, the present results indicate that both the Cr and Al concentrations and radiation defects should be considered to develop and apply the FeCrAl alloy in ATF design.

Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by the SARS-CoV-2 coronavirus. T cells play an essential role in the body’s fighting against the virus invasion, and the T cell receptor (TCR) is crucial in T cell-mediated virus recognition and clearance. However, little has been known about the features of T cell response in convalescent COVID-19 patients. In this study, using 5′RACE technology and PacBio sequencing, we analyzed the TCR repertoire of COVID-19 patients after recovery for 2 weeks and 6 months compared with the healthy donors. The TCR clustering and CDR3 annotation were exploited to discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. We first identified CD4+ and CD8+ T cell clones with certain clonal expansion after infection, and then observed the preferential recombination usage of V(D) J gene segments in CD4+ and CD8+ T cells of COVID-19 patients with different convalescent stages. More important, the TRBV6-5-TRBD2-TRBJ2-7 combination with high frequency was shared between CD4+ T and CD8+ T cells of different COVID-19 patients. Finally, we found the dominant characteristic motifs of the CDR3 sequence between recovered COVID-19 and healthy control. Our study provides novel insights on TCR in COVID-19 with different convalescent phases, contributing to our understanding of the immune response induced by SARS-CoV-2.

A stable, earth-abundant, reusable cobalt-based heterogeneous catalyst is developed for the oxidative esterification of alcohols under ambient conditions, featuring broad substrate scope, providing good to excellent product yields. This protocol enables easy recyclability of the catalyst, measured up to five times without significant loss of efficiency. The active sites of Co-N-Si/AC are proposed to be Co-N species.

In situ microanalysis of the sulfur (S) isotope composition and elemental distribution in sphalerite is important in geochemistry. A matrix-matched reference material is still lacking in situ microanalysis. In this study, a hydrothermal synthesis method combined with hot-press sintering processes was used to synthesize a sphalerite material Sph-LD. A large number of in situ microanalyses, including trace element concentrations and S isotope compositions, were performed on Sph-LD by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) to assess the homogeneity. The LA-MC-ICP-MS results are highly consistent and yield a mean δ34S value of +17.11 ± 0.20‰ (2 SD, n = 560), which is analogous with that measured by IRMS. Microanalysis of element concentrations generally agrees with the data of ICP-MS within 10% for trace elements (relative standard deviation < 10%). These results indicate that Sph-LD is suitable to be a matrix-matched reference material available for quantitative analysis of element concentrations and S isotope measurement of sphalerite using LA-ICP-MS and LA-MC-ICP-MS. Meanwhile, the synthetic method introduces a novel concept for the development of standard materials. [ABSTRACT FROM AUTHOR]