Angle-resolved transport non-reciprocity and spontaneous symmetry breaking in twisted trilayer graphene.

The identification and characterization of spontaneous symmetry breaking is central to our understanding of strongly correlated two-dimensional materials. In this work, we utilize the angle-resolved measurements of transport non-reciprocity to investigate spontaneous symmetry breaking in twisted trilayer graphene. By analysing the angular dependence of non-reciprocity in both longitudinal and transverse channels, we are able to identify the symmetry axis associated with the underlying electronic order. We report that a hysteretic rotation in the mirror axis can be induced by thermal cycles and a large current bias, supporting the spontaneous breaking of rotational symmetry. Moreover, the onset of non-reciprocity with decreasing temperature coincides with the emergence of orbital ferromagnetism. Combined with the angular dependence of the superconducting diode effect, our findings uncover a direct link between rotational and time-reversal symmetry breaking. These symmetry requirements point towards exchange-driven instabilities in momentum space as a possible origin for transport non-reciprocity in twisted trilayer graphene.

Safety and Immunogenicity of a Messenger RNA-Based Cytomegalovirus Vaccine in Healthy Adults: Results From a Phase 1 Randomized Clinical Trial.

BACKGROUND: This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, a messenger RNA (mRNA)-based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults. METHODS: Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose. RESULTS: A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (standard deviation) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus. CONCLUSIONS: This phase 1, first-in-human trial demonstrated that mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses. Clinical Trials Registration. NCT03382405.

Cytomegalovirus (CMV) is a common virus that can cause severe illness in people with weakened immune systems and in babies infected from a mother with a CMV infection during pregnancy. To date, there is no approved vaccine available to prevent CMV infection. This study in healthy adult participants is the first to test an investigational CMV vaccine called mRNA-1647, a messenger RNA (mRNA)-based vaccine developed using a technology similar to that used for vaccines to prevent COVID-19. Here, we evaluated the safety of mRNA-1647 and whether mRNA-1647 can increase levels of antibodies and immune cells (parts of the immune system that help defend against a foreign invader such as a virus). Most of the side effects observed after mRNA-1647 injection were mild; these included common reactions that occur after vaccination such as pain at the site of vaccination, headache, tiredness, muscle aches and pains, and chills. Levels of antibodies and immune cells in the blood increased after vaccination with mRNA-1647. Together, these findings show that mRNA-1647 was well tolerated and produced an immune response in adults, and support continued research on mRNA-1647 as a potential approach to prevent CMV infection.

Single-cell transcriptomics analysis of cellular heterogeneity and immune mechanisms in neurodegenerative diseases.

Single-cell transcriptomics analysis is an advanced technology that can describe the intracellular transcriptome in complex tissues. It profiles and analyses datasets by single-cell RNA sequencing. Neurodegenerative diseases are identified by the abnormal apoptosis of neurons in the brain with few or no effective therapy strategies at present, which has been a growing healthcare concern and brought a great burden to society. The transcriptome of individual cells provides deep insights into previously unforeseen cellular heterogeneity and gene expression differences in neurodegenerative disorders. It detects multiple cell subsets and functional changes during pathological progression, which deepens the understanding of the molecular underpinnings and cellular basis of neurodegenerative diseases. Furthermore, the transcriptome analysis of immune cells shows the regulation of immune response. Different subtypes of immune cells and their interaction are found to contribute to disease progression. This finding enables the discovery of novel targets and biomarkers for early diagnosis. In this review, we emphasize the principles of the technology, and its recent progress in the study of cellular heterogeneity and immune mechanisms in neurodegenerative diseases. The application of single-cell transcriptomics analysis in neurodegenerative disorders would help explore the pathogenesis of these diseases and develop novel therapeutic methods.

Testing the ectomycorrhizal-dominance hypothesis for ecosystem multifunctionality in a subtropical mountain forest.

Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time.

Intra- and Peri-tumoral Radiomics Based on Dynamic Contrast Enhanced-MRI to Identify Lymph Node Metastasis and Prognosis in Intrahepatic Cholangiocarcinoma.

BACKGROUND: Lymph node metastasis (LNM) in patients with intrahepatic cholangiocarcinoma (iCCA) affects treatment strategies and prognosis. However, preoperative imaging is not reliable enough for identifying LNM. PURPOSE: To develop and validate a radiomics nomogram based on dynamic contrast enhanced (DCE)-MR images for identifying LNM and prognosis in iCCA. STUDY TYPE: Retrospective. SUBJECTS: Two hundred four patients with pathologically proven iCCA who underwent curative-intent resection and lymphadenectomy (training cohort: N = 107, internal test cohort: N = 46, and external test cohort: N = 51). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted imaging, diffusion-weighted imaging and DCE imaging at 1.5 T or 3.0 T. ASSESSMENT: Radiomics features were extracted from intra- and peri-tumoral regions on preoperative DCE-MR images. Imaging features were evaluated by three radiologists, and significant variables in univariable and multivariable regression analysis were included in clinical model. The best-performing radiomics signature and clinical characteristics (intrahepatic duct dilatation, MRI-reported LNM) were combined to build a nomogram. Patients were divided into high-risk and low-risk groups based on their nomogram scores (cutoff = 0.341). Patients were followed up for 1-102 months (median 12) after surgery, the overall survival (OS) and recurrence-free survival (RFS) were calculated. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, calibration, decision curve, Delong test, Kaplan-Meier curves, log rank test. Two tailed P < 0.05 was considered statistically significant. RESULTS: The nomogram incorporating intra- and peri-tumoral radiomics features, intrahepatic duct dilatation and MRI-reported LNM obtained the best discrimination for LNM, with areas under the ROC curves of 0.946, 0.913, and 0.859 in the training, internal, and external test cohorts. In the entire cohort, high-risk patients had significantly lower RFS and OS than low-risk patients. High-risk of LNM was an independent factor of unfavorable OS and RFS. DATA CONCLUSION: The nomogram integrating intra- and peri-tumoral radiomics signatures has potential to identify LNM and prognosis in iCCA. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Application of nZnO supported with nanoclay for improving shrimp immunity.

This study discloses the nanoscale silicate platelet-supported nZnO (ZnONSP) applied as novel feed additives in aquaculture. The preparation of the nanohybrid (ZnO/NSP = 15/85, w/w) was characterized by UV-visible spectroscopy, powder X-ray diffraction and transmission electron microscope. The effects of ZnONSP on growth, zinc accumulation, stress response, immunity and resistance to Vibrio alginolyticus in white shrimp (Penaeus vannamei) were \demonstrated. To evaluate the safety of ZnONSP, shrimps (2.0 ± 0.3 g) were fed with ZnONSP containing diets (200, 400 and 800 mg/kg) for 56 days. Dietary ZnONSP did not affect the weight gain, specific growth rate, feed conversion ratio, survival rate, zinc accumulation, and the expression of heat shock protein 70 in tested shrimps. To examine the immunomodulatory effect of ZnONSP, shrimps (16.6 ± 2.4 g) were fed with the same experimental diets for 28 days. Dietary ZnONSP improved the immune responses of haemocyte in tested shrimps, including phagocytic rate, phagocytic index, respiratory burst, and phenoloxidase activity, and upregulated the expression of several genes, including lipopolysaccharide, ß-1,3-glucan binding protein, peroxinectin, penaeidin 2/3/4, lysozyme, crustin, anti-lipopolysaccharide factor, superoxide dismutase, glutathione peroxidase, clotting protein and α-2-macroglobulin. In the challenge experiment, shrimps (17.2 ± 1.8 g) were fed with ZnONSP containing diets (400 and 800 mg/kg) for 7 days and then infected with Vibrio alginolyticus. Notably, white shrimps that received ZnONSP (800 mg/kg) showed significantly improved Vibrio resistance, with a survival rate of 71.4 % at the end of 7-day observation. In conclusion, this study discovers that ZnONSP is a new type of immunomodulatory supplement that are effective on enhancing innate cellular and humoral immunities, and disease resistance in white shrimp.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

Developmental characteristics of aggregated lymphoid nodules area in the abomasum of fetal Bactrian camels (Camelus bactrianus).

BACKGROUND: Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . RESULTS: The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. CONCLUSIONS: Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Comparison Between a Modified Fast 3-Dimensional Turbo Spin-Echo and Diffusion-Weighted Imaging With Background Suppression in Evaluation of Lumbosacral Plexus and Its Branches.

OBJECTIVES: To compare the fast 3-dimensional NerveVIEW (3D NerveVIEW) with diffusion-weighted imaging with background suppression (DWIBS) in imaging of lumbosacral plexus and its branches. METHODS: A prospective study was performed on 30 healthy volunteers and patients who had undergone compressed sensing 3D NerveVIEW and DWIBS scans. There were 11 healthy subjects, 15 patients with lumbar disc herniation, and 4 patients with chronic inflammatory demyelinating polyradiculoneuropathy. Image quality was rated using a 4-point subjective scale. Quantitative evaluation of the nerves was done by measuring signal-to-noise ratio, contrast-to-noise ratio, and signal-to-background ratio, and the consistency in the measurements of nerve root cross-sectional areas was also assessed. The differences of signal-to-noise ratio, contrast-to-noise ratio, signal-to-background ratio, and the scores of image quality between 2 sequences were compared. RESULTS: The overall average image quality score of 3D NerveVIEW was significantly higher than that of DWIBS (2.72 ± 0.45 and 2.45 ± 0.81, respectively; P < 0.01). In terms of individual nerves, there was no significant difference between the 2 sequences in the display of the nerves from L2 to S1; however, 3D NerveVIEW was significantly better than DWIBS in demonstration of the S2-S3 nerves, as well as the nerve details. Regarding quantitative measurements, these sequences achieved comparable results with excellent interobserver agreements. CONCLUSION: Fast 3D NerveVIEW was superior to DWIBS with improved conspicuity of small distal nerves of S2-S3 and nerve details.

Vitamin E for people with non-alcoholic fatty liver disease.

RATIONALE: Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, affecting an estimated 3 in 10 people. The available treatment is far from optimal. Diet and lifestyle changes to promote weight loss and weight loss maintenance are the basic management of NAFLD, but these are difficult to achieve and maintain. Vitamin E has shown beneficial effects on oxidative stress, which plays a major role in the pathogenesis of NAFLD. However, there is uncertainty about the effects of vitamin E for people with NAFLD. OBJECTIVES: To evaluate the beneficial and harmful effects of vitamin E alone, or vitamin E in combination with other vitamins or minerals, versus placebo or no intervention in people with NAFLD. SEARCH METHODS: We used recommended Cochrane search methods. The latest search was performed on 2 February 2024. ELIGIBILITY CRITERIA: We included randomised clinical trials that compared vitamin E alone, or in combination with other vitamins or minerals, at any dose, duration, and route of administration, versus placebo or no intervention, in people with NAFLD of any age, sex, or ethnic origin. We included participants with imaging techniques or histology-proven NAFLD and minimal alcohol intake, and participants with steatohepatitis who had liver biopsies. OUTCOMES: Our critical outcomes were all-cause mortality, liver-related mortality, and serious adverse events. Our important outcomes were liver-related morbidity, health-related quality of life, non-serious adverse events, biochemical response, and imaging assessment of the degree of fatty liver. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias for each of the predefined outcomes. SYNTHESIS METHODS: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: We included 16 randomised clinical trials involving 1066 paediatric and adult participants with NAFLD. Experimental groups received vitamin E alone (14 trials) or vitamin E in combination with vitamin C (2 trials). Control groups received placebo in 13 trials and no intervention in three trials. Daily dosages of oral vitamin E ranged from 298 international units (IU) to 1000 IU. Co-interventions were lifestyle and low-calorie diet interventions in 13 trials, ursodeoxycholic acid in one trial, unchanged diet and physical activity in one trial, and baseline treatments for type 2 diabetes in one trial. Nine trials had more than two intervention groups, but we used only the groups in which vitamin E alone or vitamin E in combination with vitamin C were compared with placebo or no intervention. In total, 7.9% (84/1066) of participants dropped out. Follow-up ranged from 2 months to 24 months. SYNTHESIS OF RESULTS: Vitamin E versus placebo or no intervention The effects of vitamin E versus placebo or no intervention on all-cause mortality (risk ratio (RR) 3.45, 95% confidence interval (CI) 0.57 to 20.86; 3 trials, 351 participants; very low certainty evidence) and serious adverse events (RR 1.91, 95% CI 0.30 to 12.01; 2 trials, 283 participants; very low certainty evidence) are very uncertain. There were no data on liver-related mortality or liver-related morbidity. The effects of vitamin E versus placebo or no intervention on physical health-related quality of life (mean difference (MD) 0.74, 95% CI -0.52 to 2.01; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); psychosocial health-related quality of life (MD -0.57, 95% CI -4.11 to 2.97; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); and non-serious adverse events (RR 0.86, 95% CI 0.64 to 1.17; 2 trials, 283 participants; very low certainty evidence) are also very uncertain. There were no data on proportion of participants without a decrease in liver enzymes. Vitamin E likely slightly reduces serum alanine transaminase (ALT) (MD -9.29, 95% CI -13.69 to -4.89; 11 trials, 708 participants; moderate certainty evidence) and aspartate aminotransferase (AST) (MD -4.90, 95% CI -7.24 to -2.57; 11 trials, 695 participants; moderate certainty evidence) levels compared with placebo or no intervention. Vitamin E may slightly reduce serum alkaline phosphatase (ALP) levels (MD -5.21, 95% CI -9.88 to -0.54; 5 trials, 416 participants; very low certainty evidence), but the evidence is very uncertain. Vitamin E plus vitamin C versus placebo There were no data on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, and non-serious adverse events. The effects of vitamin E plus vitamin C on reducing serum ALT (MD -0.50, 95% CI -4.58 to 3.58; 2 trials, 133 participants; very low certainty evidence), AST (MD 0.09, 95% CI -3.39 to 3.57; 1 trial, 88 participants; very low certainty evidence), and gamma-glutamyl transferase (GGT) levels (MD 1.58, 95% CI -3.22 to 6.38; 1 trial, 88 participants; very low certainty evidence) are very uncertain. We identified three ongoing trials, and six trials are awaiting classification. AUTHORS' CONCLUSIONS: Given the very low certainty evidence, we do not know if long-term treatment (18 months to 24 months) with vitamin E administered alone affects all-cause mortality, serious adverse events, quality of life, or non-serious adverse events in people with NAFLD when compared with placebo or no intervention. We found no data on liver-related mortality, liver-related morbidity, or proportion of participants without a decrease in liver enzymes. Vitamin E likely reduces ALT and AST slightly when compared with placebo, but whether this has any impact on the clinical course in people with NAFLD is unknown. The trials on vitamin E plus vitamin C did not report on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, or non-serious adverse events. Given the very low certainty evidence, we do not know the effects of vitamin E plus vitamin C on liver enzymes in people with NAFLD when compared with placebo. FUNDING: Three trials disclosed no external funding. Five trials were industry funded. Five trials were funded by organisations with no vested interests. Three trials did not provide any information on clinical trial support or sponsorship. REGISTRATION: Protocol: doi.org/10.1002/14651858.CD015033.

Prokaryotic Expression, Purification, and Biological Properties of a Novel Bioactive Protein (PFAP-1) from Pinctada fucata.

Pinctada fucata meat is the main by-product of the pearl harvesting industry. It is rich in nutrition, containing a lot of protein and peptides, and holds significant value for both medicine and food. In this study, a new active protein was discovered and expressed heterogeneously through bioinformatics analysis. It was then identified using Western blot, molecular weight, and mass spectrometry. The antibacterial activity, hemolysis activity, antioxidant activity, and Angiotensin-Converting Enzyme II (ACE2) inhibitory activity were investigated. An unknown functional protein was screened through the Uniprot protein database, and its primary structure did not resemble existing proteins. It was an α-helical cationic polypeptide we named PFAP-1. The codon-optimized full-length PFAP-1 gene was synthesized and inserted into the prokaryotic expression vector pET-30a. The induced expression conditions were determined with a final isopropyl-ß-d-thiogalactoside (IPTG) concentration of 0.2 mM, an induction temperature of 15 °C, and an induction time of 16 h. The recombinant PFAP-1 protein, with low endotoxin and sterility, was successfully prepared. The recombinant PFAP-1 protein exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, and the diameter of the inhibition zone was 15.99 ± 0.02 mm. Its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 37.5 µg/mL and 150 µg/mL, respectively, and its hemolytic activity was low (11.21%) at the bactericidal concentration. The recombinant PFAP-1 protein significantly inhibited the formation of MRSA biofilm and eradicated MRSA biofilm. It also demonstrated potent 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) scavenging activity with a half-maximal inhibitory concentration (IC50) of 40.83 µg/mL. The IC50 of ACE2 inhibition was 5.66 µg/mL. Molecular docking results revealed that the optimal docking fraction of PFAP-1 protein and ACE2 protein was -267.78 kcal/mol, with a confidence level of 0.913. The stable binding complex was primarily formed through nine groups of hydrogen bonds, three groups of salt bridges, and numerous hydrophobic interactions. In conclusion, recombinant PFAP-1 can serve as a promising active protein in food, cosmetics, or medicine.

Molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce (Lactuca sativa L.) after ultrasound treatment at different intensity levels.

Ultrasonic treatment is widely used for surface cleaning of vegetables in the processing of agricultural products. In the present study, the molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce was investigated after ultrasound treatment at different intensity levels. The results show that the biofilm was efficiently removed after ultrasound treatment with intensity higher than 21.06 W/cm2. However, at an intensity of less than 18.42 W/cm2, P. fluorescens was stimulated by ultrasound leading to promoted bacterial growth, extracellular protease activity, extracellular polysaccharide secretion (EPS), and synthesis of acyl-homoserine lactones (AHLs) as quorum-sensing signaling molecules. The expression of biofilm-related genes, stress response, and dual quorum sensing system was upregulated during post-treatment ultrasound. Proteomic analysis showed that ultrasound activated proteins in the flagellar system, which led to changes in bacterial tendency; meanwhile, a large number of proteins in the dual-component system began to be regulated. ABC transporters accelerated the membrane transport of substances inside and outside the cell membrane and equalized the permeability conditions of the cell membrane. In addition, the expression of proteins related to DNA repair was upregulated, suggesting that bacteria repair damaged DNA after ultrasound exposure.

Load Prediction in Double-Channel Residual Self-Attention Temporal Convolutional Network with Weight Adaptive Updating in Cloud Computing.

When resource demand increases and decreases rapidly, container clusters in the cloud environment need to respond to the number of containers in a timely manner to ensure service quality. Resource load prediction is a prominent challenge issue with the widespread adoption of cloud computing. A novel cloud computing load prediction method has been proposed, the Double-channel residual Self-attention Temporal convolutional Network with Weight adaptive updating (DSTNW), in order to make the response of the container cluster more rapid and accurate. A Double-channel Temporal Convolution Network model (DTN) has been developed to capture long-term sequence dependencies and enhance feature extraction capabilities when the model handles long load sequences. Double-channel dilated causal convolution has been adopted to replace the single-channel dilated causal convolution in the DTN. A residual temporal self-attention mechanism (SM) has been proposed to improve the performance of the network and focus on features with significant contributions from the DTN. DTN and SM jointly constitute a dual-channel residual self-attention temporal convolutional network (DSTN). In addition, by evaluating the accuracy aspects of single and stacked DSTNs, an adaptive weight strategy has been proposed to assign corresponding weights for the single and stacked DSTNs, respectively. The experimental results highlight that the developed method has outstanding prediction performance for cloud computing in comparison with some state-of-the-art methods. The proposed method achieved an average improvement of 24.16% and 30.48% on the Container dataset and Google dataset, respectively.

A Novel Frameshift Mutation of HBB Causing Dominant ß-Thalassemia in a Chinese Individual.

We reported a rare ß-thalassemia patient, a 41-year-old Chinese male with small cell hypopigmentation anemia, jaundice and splenomegaly as the main clinical symptoms. By using Next-Generation Sequencing (NGS), we identified a novel de novo HBB mutation(c.358_365dup, p.Phe123Alafs*39) which resulted in an abnormally prolonged ß-globin chain comprising 159 amino acid residues. The secondary and three-dimensional structures of the ß-globin predicted that the novel prolonged ß-globin chain has a considerable risk of instability in the hemoglobin, and leads to clinical phenotype. This study contributes to the enrichment of the genetic pathogenic mutation database for thalassemia and underscores the significance of NGS in the screening of mutations for thalassemia families.

[Traditional Chinese medicine and active ingredients regulate M1/M2 macrophage polarization balance to treat chronic obstructive pulmonary disease: a review].

Chronic obstructive pulmonary disease(COPD) is a progressive lung dysfunction(disease) caused by long-term inhalation of toxic particles, especially smoking. The continued exposure to harmful substances triggers an abnormal inflammatory response, which causes permanent damage to the respiratory system, ultimately leading to irreversible pathological changes. Lung macrophages(LMs) are key innate immune effectors involved in the recognition, phagocytosis, and clearance of pathogens, as well as in the processing of inhaled hazardous particulate matter(e. g., cigarette smoke and particulate matter). LMs are polarized toward the M1 or M2 phenotype in response to the activation of inflammatory mediators to exert pro-/anti-inflammatory effects, respectively, thus being involved in the pulmonary parenchymal damage(emphysema) and repair(airway remodeling) throughout the process of COPD.In addition, they are responsible for phagocytosis and clearance of apoptotic or necrotic tissue cells, which helps to maintain the stability of the microenvironment in the lungs of COPD patients. Modern studies have revealed that macrophage polarization plays a pivotal role in the pathogenesis and development of COPD and is considered a potential target for treating COPD because of its ability to reduce airway inflammation, inhibit tissue remodeling, and combat oxidative stress. In recent years, traditional Chinese medicine(TCM) and its active ingredients have become a hot area in the treatment of COPD by targeting the balance of M1/M2 macrophage polarization. TCM and its active ingredients can intervene in the inflammatory response to promote the repair of the lung tissue in the patients with COPD. This paper reviews the research achievements of TCM and its active ingredients in this field in recent years,aiming to provide a scientific basis and strong support for the precise diagnosis and treatment of COPD.

Time-of-Flight Intracranial MRA at 3 T versus 5 T versus 7 T: Visualization of Distal Small Cerebral Arteries.

Background Three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) at 7 T has been reported to have high image quality for visualizing small perforating vessels. However, B1 inhomogeneity and more physiologic considerations limit its applications. Angiography at 5 T may provide another choice for intracranial vascular imaging. Purpose To evaluate the image quality and cerebrovascular visualization of 5-T 3D TOF MRA for visualizing intracranial small branch arteries. Materials and Methods Participants (healthy volunteers or participants with a history of ischemic stroke undergoing intracranial CT angiography or MRA for identifying steno-occlusive disease) were prospectively included from September 2021 to November 2021. Each participant underwent 3-T, 5-T, and 7-T 3D TOF MRA with use of customized MR protocols within 48 hours. Radiologist scoring from 0 (invisible) to 3 (excellent) and quantitative assessment were obtained to evaluate the image quality. The Friedman test was used for comparison of characteristics derived from 3 T, 5 T, and 7 T. Results A total of 12 participants (mean age ± SD, 38 years ± 9; nine men) were included. Visualizations of the distal arteries and small vessels at 5-T TOF MRA were significantly higher than those at 3 T (median score: 3.0 vs 2.0, all P < .001 for distal segments and lenticulostriate artery; median score: 2.0 vs 0, P < .001 for pontine artery). The total length of small vessel branches detected at 5 T was larger than that at 3 T (5.1 m ± 0.7 vs 1.9 m ± 0.4; P < .001). However, there was no evidence of a significant difference compared with 7 T in either the depiction of distal segments and small vessel branches (average median score, 2.5; all P > .05) or the quantitative measurements (total length, 5.6 m ± 0.5; P = .41). Conclusion Three-dimensional time-of-flight MR angiography at 5 T presented the capability to provide superior visualization of distal large arteries and small vessel branches (in terms of subjective and quantitative assessment) to 3 T and had image quality similar to 7 T. © RSNA, 2022 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on September 14, 2022.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Bacterial diversity and community characteristics of the sinus and dental regions in adults with odontogenic sinusitis.

BACKGROUND: The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion samples were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted tooth extraction patients. DNA was extracted, and 16S rRNA sequencing was performed to explore the characteristics and structure of the microbiome in the sinuses and dental regions of OS patients. RESULTS: The alpha diversity of the oral and nasal microbiomes in OS patients was higher than that in controls. Principal coordinate analysis (PCoA) showed that oral samples clustered separately from nasal samples, and the beta diversity of oral and nasal samples in OS patients was higher than that in controls. The dominant phylum was Bacteroidetes in OS patients and Firmicutes in controls in both the oral and nasal cavity. The dominant genera in the oral microbiome and nasal microbiome of OS patients were similar, including Fusobacterium, Porphyromonas and Prevotella. Co-occurrence network analysis showed decreased microbial connectivity in the oral mucosa and nasal secretion samples of OS patients. CONCLUSIONS: Odontogenic infection promotes structural and functional disorders of the nasal microbiome in OS. The interaction of dominant pathogens in the nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS.

Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study.

OBJECTIVE: This study aimed to compare the efficacy and safety of adalimumab (ADA) versus tocilizumab (TCZ) in patients with Takayasu arteritis (TAK). METHODS: This was a randomized, controlled, open-label study. Forty patients with active and severe TAK were enrolled. They were treated with ADA (n = 21) combined with glucocorticoids (GCs) and methotrexate (MTX) or TCZ (n = 19) combined with GCs and MTX. The planned follow-up duration was 12 months. The primary end point was the efficacy rate (ER) at 6 months. The secondary endpoints included ER at 9 and 12 months, relapse rate, GC tapering, adverse effects, and life quality changes during treatment. RESULTS: In the intention-to-treat (ITT) population, the ER at 6 months was higher in the ADA group (85.71% vs 52.63%, P= 0.02). A similar direction of effect was noted in the per-protocol set (89.47% vs 62.50%, P= 0.06). The percentages of patients who achieved a GC dose of ≤ 10 mg/day at 6 months were similar between the ADA and TCZ groups (47.37% vs 43.75%, P= 0.83). The ERs at 9 and 12 months were similar between the two groups (P> 0.05). During the first 12 months of treatment, the relapse rate and adverse event incidence were comparable between the two groups (ADA vs TCZ: 9.52% vs 10.53%, P= 0.96; 38.10% vs 47.37%, P= 0.55, respectively). CONCLUSION: ADA combined with GCs and MTX may be more efficacious than TCZ combined with GCs and MTX among patients with active and severe TAK. TRIAL REGISTRATION: Clinicaltrials.gov; NCT04300686.

Prediction of new cerebral ischemic lesion after carotid artery stenting: a high-resolution vessel wall MRI-based radiomics analysis.

OBJECTIVES: Carotid artery stenting (CAS) is an established treatment for local stenosis. The most common complication is new ipsilateral ischemic lesions (NIILs). This study aimed to develop models considering lesion morphological and compositional features, and radiomics to predict NIILs. MATERIALS AND METHODS: One hundred and forty-six patients who underwent brain MRI and high-resolution vessel wall MR imaging (hrVWI) before and after CAS were retrospectively recruited. Lumen and outer wall boundaries were segmented on hrVWI as well as atherosclerotic components. A traditional model was constructed with patient clinical information, and lesion morphological and compositional features. Least absolute shrinkage and selection operator algorithm was performed to determine key radiomics features for reconstructing a radiomics model. The model in predicting NIILs was trained and its performance was tested. RESULTS: Sixty-one patients were NIIL-positive and eighty-five negative. Volume percentage of intraplaque hemorrhage (IPH) and patients' clinical presentation (symptomatic/asymptomatic) were risk factors of NIILs. The traditional model considering these two features achieved an area under the curve (AUC) of 0.778 and 0.777 in the training and test cohorts, respectively. Twenty-two key radiomics features were identified and the model based on these features achieved an AUC of 0.885 and 0.801 in the two cohorts. The AUCs of the combined model considering IPH volume percentage, clinical presentation, and radiomics features were 0.893 and 0.842 in the training and test cohort respectively. CONCLUSIONS: Compared with traditional features (clinical and compositional features), the combination of traditional and radiomics features improved the power in predicting NIILs after CAS. KEY POINTS: • Volume percentage of IPH and symptomatic events were independent risk factors of new ipsilateral ischemic lesions (NIILs). • Radiomics features derived from carotid artery high-resolution vessel wall imaging had great potential in predicting NIILs after CAS. • The combination model with radiomics and traditional features further improved the diagnostic performance than traditional features alone.