Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Livestock grazing modifies soil nematode body size structure in mosaic grassland habitats.

Body size is closely related to the trophic level and abundance of soil fauna, particularly nematodes. Therefore, size-based analyses are increasingly prominent in unveiling soil food web structure and its responses to anthropogenic disturbances, such as livestock grazing. Yet, little is known about the effects of different livestock on the body size structure of soil nematodes, especially in grasslands characterized by local habitat heterogeneity. A four-year field grazing experiment from 2017 to 2020 was conducted in a meadow steppe characterized by typical mosaics of degraded hypersaline patches and undegraded hyposaline patches to assess the impacts of cattle and sheep grazing on the body size structure of soil nematodes within and across trophic groups. Without grazing, the hypersaline patches harbored higher abundance of large-bodied nematodes in the community compared to the hyposaline patches. Livestock grazing decreased large-bodied nematodes within and across trophic groups mainly by reducing soil microbial biomass in the hypersaline patches, with sheep grazing resulting in more substantial reductions compared to cattle grazing. The reduction in large-bodied nematode individuals correspondingly resulted in decreases in nematode community-weighted mean (CWM) body size, nematode biomass, and size spectra slopes. However, both cattle and sheep grazing had minimal impacts on the CWM body size and size spectra of total nematodes in the hyposaline patches. Our findings suggest that livestock grazing, especially sheep grazing, has the potential to simplify soil food webs by reducing large-bodied nematodes in degraded habitats, which may aggravate soil degradation by weakening the bioturbation activities of soil fauna. In light of the widespread land use of grasslands by herbivores of various species and the ongoing global grassland degradation of mosaic patches, the recognition of the trends revealed by our findings is critical for developing appropriate strategies for grassland grazing management.

Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

BACKGROUND: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases. The present study aimed to further investigate the roles of ADAMTS family members in aortic valve development and BAV formation. METHODS: Morpholino-based ADAMTS family gene-targeted screening for zebrafish heart outflow tract phenotypes combined with DNA sequencing in a 304 cohort BAV patient registry study was initially carried out to identify potentially related genes. Both ADAMTS gene-specific fluorescence in situ hybridization assay and genetic tracing experiments were performed to evaluate the expression pattern in the aortic valve. Accordingly, related genetic mouse models (both knockout and knockin) were generated using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) method to further study the roles of ADAMTS family genes. The lineage-tracing technique was used again to evaluate how the cellular activity of specific progenitor cells was regulated by ADAMTS genes. Bulk RNA sequencing was used to investigate the signaling pathways involved. Inducible pluripotent stem cells derived from both BAV patients and genetic mouse tissue were used to study the molecular mechanism of ADAMTS. Immunohistochemistry was performed to examine the phenotype of cardiac valve anomalies, especially in the extracellular matrix components. RESULTS: ADAMTS genes targeting and phenotype screening in zebrafish and targeted DNA sequencing on a cohort of patients with BAV identified ADAMTS16 (a disintegrin and metalloproteinase with thrombospondin motifs 16) as a BAV-causing gene and found the ADAMTS16 p. H357Q variant in an inherited BAV family. Both in situ hybridization and genetic tracing studies described a unique spatiotemporal pattern of ADAMTS16 expression during aortic valve development. Adamts16+/- and Adamts16+/H355Q mouse models both exhibited a right coronary cusp-noncoronary cusp fusion-type BAV phenotype, with progressive aortic valve thickening associated with raphe formation (fusion of the commissure). Further, ADAMTS16 deficiency in Tie2 lineage cells recapitulated the BAV phenotype. This was confirmed in lineage-tracing mouse models in which Adamts16 deficiency affected endothelial and second heart field cells, not the neural crest cells. Accordingly, the changes were mainly detected in the noncoronary and right coronary leaflets. Bulk RNA sequencing using inducible pluripotent stem cells-derived endothelial cells and genetic mouse embryonic heart tissue unveiled enhanced FAK (focal adhesion kinase) signaling, which was accompanied by elevated fibronectin levels. Both in vitro inducible pluripotent stem cells-derived endothelial cells culture and ex vivo embryonic outflow tract explant studies validated the altered FAK signaling. CONCLUSIONS: Our present study identified a novel BAV-causing ADAMTS16 p. H357Q variant. ADAMTS16 deficiency led to BAV formation.

mROS­calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia.

Lethal ventricular arrhythmia­sudden cardiac death (LVA­SCD) occurs frequently during the early stage of myocardial ischemia (MI). However, the mechanism underlying higher LVA­SCD incidence is still poorly understood. The present study aimed to explore the role of mitochondrial reactive oxygen species (mROS) and Ca2+ crosstalk in promoting LVA­SCD in early MI. RyR2 S2814A mice and their wild­type littermates were used. MitoTEMPO was applied to scavenge mitochondrial ROS (mROS). Mice were subjected to severe MI and the occurrence of LVA­SCD was evaluated. Levels of mitochondrial ROS and calcium (mitoCa2+), cytosolic ROS (cytoROS), and calcium (cytoCa2+), RyR2 Ser­2814 phosphorylation, CaMKII Met­282 oxidation, mitochondrial membrane potential (MMP), and glutathione/oxidized glutathione (GSH/GSSG) ratio in the myocardia were detected. Dynamic changes in mROS after hypoxia were investigated using H9c2 cells. Moreover, the myocardial phosphoproteome was analyzed to explore the related mechanisms facilitating mROS­Ca2+ crosstalk and LVA­SCD. There was a high incidence (~33.9%) of LVA­SCD in early MI. Mice who underwent SCD displayed notably elevated levels of myocardial ROS and mROS, and the latter was validated in H9c2 cells. These mice also demonstrated overloads of cytoplasmic and mitochondrial Ca2+, decreased MMP and reduced GSH/GSSG ratio, upregulated RyR2­S2814 phosphorylation and CaMKII­M282 oxidation and transient hyperphosphorylation of mitochondrial proteomes in the myocardium. mROS­specific scavenging by a mitochondria­targeted antioxidant agent (MitoTEMPO) corrected these SCD­induced alterations. S2814A mice with a genetically inactivated CaMKII phosphorylation site in RyR2 exhibited decreased overloads in cytoplasmic and mitochondrial Ca2+ and demonstrated similar effects as MitoTEMPO to correct SCD­induced changes and prevent SCD post­MI. The data confirmed crosstalk between mROS and Ca2+ in promoting LVA­SCD. Therefore, we provided evidence that there is a higher incidence of LVA­SCD in early MI, which may be attributed to a positive feedback loop between mROS and Ca2+ imbalance.

Changes in the airway microbiome in patients with bronchiectasis.

This study used metagenomic next-generation sequencing (mNGS) technology to explore the changes of the microbial characteristics in the lower respiratory tract in patients with acute exacerbations of bronchiectasis (noncystic fibrosis) to guide clinical treatment and improve patients' quality of life and prognosis. This prospective study included 54 patients with acute exacerbation and 46 clinically stable patients admitted to the Respiratory and Critical Care Medicine Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to July 2022. Sputum was subjected to routine microbiological tests, and bronchoalveolar lavage fluid (BALF) samples were subjected to microbiological tests and mNGS of BALF before empirical antibiotic therapy. Serum inflammatory markers (white blood cell count, interleukin-6, procalcitonin, and C-reactive protein) were measured. In addition, we evaluated the pathogen of mNGS and compared the airway microbiome composition of patients with acute exacerbation and control patients. The mean age of our cohort was 56 ±â€…15.2 years. Eighty-nine patients had positive results by mNGS. There was a significant difference in the detection of viruses between the groups (χ2 = 6.954, P < .01). The fungal species Candida albicans, Pneumocystis jirovecii, and Aspergillus fumigatus were significantly more common in patients with acute exacerbations (χ2 = 5.98, P = .014). The bacterial species Acinetobacter baumannii, Mycobacterium tuberculosis, Haemophilus influenzae, Haemophilus parahaemolyticus, Abiotrophia defectiva, and Micromonas micros were significantly more prevalent in patients with acute exacerbations (χ2 = 4.065, P = .044). The most common bacterial species isolated from the sputum and BALF samples of patients with acute exacerbation was A. baumannii. Chlamydia psittaci was found in 4 patients. In addition, of 77 patients with negative sputum culture, 66 had positive results by mNGS, demonstrating the increased sensitivity and accuracy of mNGS. Patients with acute exacerbation of bronchiectasis tend to have mixed infections in the lower respiratory tract. The frequency of viruses, fungi, and Mycoplasma was higher in these patients. Our findings suggest that mNGS could be used to identify pathogenic microorganisms in these patients, increasing the effectiveness of antibiotic therapy.

FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1.

BACKGROUND AND AIMS: NAFLD comprises a spectrum of liver disorders with the initial abnormal accumulation of lipids in hepatocytes called NAFL, progressing to the more serious NASH in a subset of individuals. Our previous study revealed that global flavin-containing monooxygenase 2 (FMO2) knockout causes higher liver weight in rats. However, the role of FMO2 in NAFLD remains unclear. Herein, we aimed to determine the function and mechanism of FMO2 in liver steatosis and steatohepatitis. APPROACH AND RESULTS: The expression of FMO2 was significantly downregulated in patients with NAFL/NASH and mouse models. Both global and hepatocyte-specific knockout of FMO2 resulted in increased lipogenesis and severe hepatic steatosis, inflammation, and fibrosis, whereas FMO2 overexpression in mice improved NAFL/NASH. RNA sequencing showed that hepatic FMO2 deficiency is associated with impaired lipogenesis in response to metabolic challenges. Mechanistically, FMO2 directly interacts with SREBP1 at amino acids 217-296 competitively with SREBP cleavage-activating protein (SCAP) and inhibits SREBP1 translocation from the endoplasmic reticulum (ER) to the Golgi apparatus and its subsequent activation, thus suppressing de novo lipogenesis (DNL) and improving NAFL/NASH. CONCLUSIONS: In hepatocytes, FMO2 is a novel molecule that protects against the progression of NAFL/NASH independent of enzyme activity. FMO2 impairs lipogenesis in high-fat diet-induced or choline-deficient, methionine-deficient, amino acid-defined high-fat diet-induced steatosis, inflammation, and fibrosis by directly binding to SREBP1 and preventing its organelle translocation and subsequent activation. FMO2 thus is a promising molecule for targeting the activation of SREBP1 and for the treatment of NAFL/NASH.

Women with preeclampsia may have reduced risk of breast cancer: a meta-analysis of cohort studies with 7.8 million participants.

This review pooled data from the literature to examine the association between preeclampsia (PE) and subsequent risk of breast cancer in women. Cohort studies published in the databases of PubMed, Embase, Scopus, and Web of Science up to 18 July 2023 were searched. Adjusted data were pooled to obtain the risk ratio (RR). Eleven studies with 15 cohorts and a cumulative sample size of 7,838,693 women were included. Meta-analysis of all studies demonstrated a reduced risk of breast cancer in women with PE as compared to those without PE (RR: 0.89 95% CI: 0.83, 0.95 p < 0.001 I2 = 50%). Follow-up ranged from 8 to 29.2 years. Results did not change during sensitivity analysis. Outcomes varied on subgroup analysis based on location, study type, data extraction method, incidence of breast cancer, and follow-up. To conclude, women with PE may have a reduced risk of breast cancer later in life. However, the risk reduction is minimal and may not have much clinical significance. The evidence is also limited by high inter-study heterogeneity and lack of adjustment of all possible confounders.

Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma.

Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis­related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis­related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis­related genes in HCC.

Clinical application of modified hip joint lateral position in femoral neck fracture.

BACKGROUND: To show the femoral neck better in hip lateral view of X-ray, we design a modified hip lateral view and then investigate the value in femoral neck fractures. METHODS: CT images of 10 normal hip joints for 3D reconstruction were selected, the Mimics Medical 21.0 was used, and rotating the proximal femur was to find the most suitable angle for showing the femoral neck well, designed the modified lateral view according to this angle. We collected 35 healthy cases and 35 femoral neck fractures as the normal and fracture group. And two groups were all taken hip anteroposterior view, cross-table lateral view and modified lateral view, which were analyzed by two radiologists to score the anatomical structures of the articular surface, femoral head, head neck junction, femoral neck, basal region and intertrochanteric region. Friedman test was used to analyze the score of femoral neck at different angles. T test and Wilcoxon signed-rank test were to compare inter-groups. RESULTS: The modified lateral view was designed as follows: The subjects were supine, with the sagittal axis biased toward the healthy side at an angle of approximately 20° to the long axis of the examination table, the hip joint flexed at 45°, the lower extremity abducted at 40°, the centerline inclined 45° toward the head and the centerline aligned with the center of the groin. The modified lateral view showed the femoral head, head neck junction and femoral neck more clearly than the cross-table lateral view, but the cross-table lateral view showed the femoral neck basal and intertrochanteric region better. In addition, the time of taking the modified lateral view was significantly less than the cross-table lateral view (normal group: 0.789 min ± 0.223 vs 0.623 min ± 0.207, P < 0.001; fracture group: 1.131 min ± 0.362 vs 0.946 min ± 0.390, P < 0.001). CONCLUSIONS: The modified lateral view can obtain a standard sagittal image of femoral neck, which can show the dislocation and angulation of the sagittal femoral neck fracture clearly, and improve the accuracy of diagnosis. And it is more convenient and easier for patients to cooperate, which is worthy promoting and applying in clinical work.

Clinical Evaluation of Metagenomic Next-Generation Sequencing and Identification of Risk Factors in Patients with Severe Community-Acquired Pneumonia.

Purpose: Severe community-acquired pneumonia (SCAP) is the leading cause of death among patients with infectious diseases worldwide. This study aimed to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) through detecting pathogens in bronchoalveolar lavage fluid (BALF) and identifying risk factors for recovery in SCAP patients. Patients and Methods: This prospective study recruited 158 SCAP patients admitted to respiratory intensive care unit that were randomly divided into control and study groups, with receiving conventional tests and the same conventional tests plus mNGS, respectively. The diagnostic efficiency of mNGS was evaluated by comparing with conventional tests. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for recovery in SCAP patients, and a nomogram prediction model was established based on these factors. Results: Within the study group, the pathogen detection rate was significantly higher with mNGS than that with conventional tests (84.81% vs 45.57%, P < 0.001), with a positive coincidence rate of 94.44%. Acinetobacter baumannii (21.52%, 17/79), Candida albicans (17.72%, 14/79), and Klebsiella pneumonia (15.19%, 12/79) were the top three common pathogens detected by mNGS. Of note, the improvement rate of patients in the study group was significantly higher than that in the control group. The further analysis revealed that the increased levels of interleukin-6, blood urea nitrogen, procalcitonin, the longer length of hospital stay, and bacterial infection were independent risk factors for recovery of SCAP patients, while mNGS detection status was a protective factor. The predictive model showed a good performance for the modeling and validation sets. Conclusion: Early mNGS exhibited a superior diagnostic efficiency to conventional tests in SCAP patients, which can reduce the risk of death in SCAP patients. Moreover, the clinical factors could also be used for the management and prognosis prediction of SCAP patients.

Chromosomal Aberrations in Pediatric Patients With Moderate/Severe Developmental Delay/Intellectual Disability With Abundant Phenotypic Heterogeneities: A Single-Center Study.

BACKGROUND: This study aimed to examine the clinical usefulness of chromosome microarray (CMA) for selective implementation in patients with unexplained moderate or severe developmental delay/intellectual disability (DD/ID) and/or combined with different dysphonic features in the Han Chinese population. METHODS: We retrospectively analyzed data on 122 pediatric patients with unexplained isolated moderate/severe DD/ID with or without autism spectrum disorders, epilepsy, dystonia, and congenital abnormalities from a single-center neurorehabilitation clinic in southern China. RESULTS: A total of 46 probands (37.7%) had abnormal CMA results among the 122 study patients. With the exclusion of aneuploidies, uniparental disomies, and multiple homozygotes, 37 patients harbored 39 pathogenic copy number variations (pCNVs) (median [interquartile range] size: 3.57 [1.6 to 7.1] Mb; 33 deletions and 6 duplications), enriched in chromosomes 5, 7, 15, 17, and 22, with a markedly high prevalence of Angelman/Prader-Willi syndrome (24.3% [nine of 37]). Three rare deletions in the regions 5q33.2q34, 17p13.2, and 13q33.2 were reported, with specific delineation of clinical phenotypes. The frequencies of pCNVs were 18%, 33.3%, 38.89%, 41.67%, and 100% for patients with 1, 2, 3, 4, and 5 study phenotypes, respectively; patients with more concomitant abnormalities in the heart, brain, craniofacial region, and/or other organs had a higher CMA diagnostic yield and pCNV prevalence (P < 0.05). CONCLUSIONS: Clinical application of CMA as a first-tier test among patients with moderate/severe DD/ID combined with congenital structural anomalies improved diagnostic yields and the quality of clinical management in this series of patients.

Fear of predators alters herbivore regulation of soil microbial community function.

Fear of predation can affect important ecosystem processes by altering the prey traits expression that, in turn, regulates the quantity and quality of nutritional inputs to soil. Here, we aimed to assist in bridging a knowledge gap in this cascading chain of events by exploring how risk of spider predation may affect grasshopper prey performances, and the activity of various microbial extracellular enzymes in the soil. Using a mesocosms field-experiment, we found that grasshoppers threatened by spider predation ate less, grew slower, and had a higher body carbon to nitrogen ratio. Herbivory increased activity of all microbial extracellular enzymes examined, likely due to higher availability of root exudates. Predation risk had no effect on C-acquiring enzymes but decreased activity of P-acquiring enzymes. We found contrasting results regarding the effect of predation on the activity of N-acetyl-glucosaminidase and leucine arylamidase N-acquiring enzymes, suggesting that predation risk may alter the composition of N-inputs to soil. Our work highlighted the importance of soil microbial enzymatic activity as a way to predict how changes in the aboveground food-web dynamics may alter key ecosystem processes like nutritional-cycling.

Metabolomics acts as a powerful tool for comprehensively evaluating vaccines approved under emergency: a CoronaVac retrospective study.

Introduction: To control the COVID-19 pandemic, great efforts have been made to realize herd immunity by vaccination since 2020. Unfortunately, most of the vaccines against COVID-19 were approved in emergency without a full-cycle and comprehensive evaluation process as recommended to the previous vaccines. Metabolome has a close tie with the phenotype and can sensitively reflect the responses to stimuli, rendering metabolomic analysis have the potential to appraise and monitor vaccine effects authentically. Methods: In this study, a retrospective study was carried out for 330 Chinese volunteers receiving recommended two-dose CoronaVac, a vaccine approved in emergency in 2020. Venous blood was sampled before and after vaccination at 5 separate time points for all the recipients. Routine clinical laboratory analysis, metabolomic and lipidomic analysis data were collected. Results and discussion: It was found that the serum antibody-positive rate of this population was around 81.82%. Most of the laboratory parameters were slightly perturbated within the relevant reference intervals after vaccination. The metabolomic and lipidomic analyses showed that the metabolic shift after inoculation was mainly in the glycolysis, tricarboxylic acid cycle, amino acid metabolism, urea cycle, as well as microbe-related metabolism (bile acid metabolism, tryptophan metabolism and phenylalanine metabolism). Time-course metabolome changes were found in parallel with the progress of immunity establishment and peripheral immune cell counting fluctuation, proving metabolomics analysis was an applicable solution to evaluate immune effects complementary to traditional antibody detection. Taurocholic acid, lysophosphatidylcholine 16:0 sn-1, glutamic acid, and phenylalanine were defined as valuable metabolite markers to indicate the establishment of immunity after vaccination. Integrated with the traditional laboratory analysis, this study provided a feasible metabolomics-based solution to relatively comprehensively evaluate vaccines approved under emergency.

Deep Attentional Guided Image Filtering.

Guided filter is a fundamental tool in computer vision and computer graphics, which aims to transfer structure information from the guide image to the target image. Most existing methods construct filter kernels from the guidance itself without considering the mutual dependency between the guidance and the target. However, since there typically exist significantly different edges in two images, simply transferring all structural information from the guide to the target would result in various artifacts. To cope with this problem, we propose an effective framework named deep attentional guided image filtering, the filtering process of which can fully integrate the complementary information contained in both images. Specifically, we propose an attentional kernel learning module to generate dual sets of filter kernels from the guidance and the target and then adaptively combine them by modeling the pixelwise dependency between the two images. Meanwhile, we propose a multiscale guided image filtering module to progressively generate the filtering result with the constructed kernels in a coarse-to-fine manner. Correspondingly, a multiscale fusion strategy is introduced to reuse the intermediate results in the coarse-to-fine process. Extensive experiments show that the proposed framework compares favorably with the state-of-the-art methods in a wide range of guided image filtering applications, such as guided super-resolution (SR), cross-modality restoration, and semantic segmentation. Moreover, our scheme achieved the first place in the real depth map SR challenge held in ACM ICMR 2021. The codes can be found at https://github.com/zhwzhong/DAGF.

Parasites as ecosystem modulators: foliar pathogens suppress top-down effects of large herbivores.

Parasites can catalyze or inhibit interactions between their hosts and other species, but the ecosystem-level effects of such interaction modifications are poorly understood. We conducted a large-scale field experiment in temperate grasslands of China to understand how foliar fungal pathogens influenced top-down effects of cattle on plant diversity and productivity. When foliar pathogens were suppressed, cattle grazing strongly reduced biomass of the dominant grass, Leymus chinensis, generating competitive release that significantly increased community-level species richness and evenness. In the absence of grazing, pathogen attack on L. chinensis had no measurable effect on host biomass. However, pathogens disrupted top-down effects of herbivory by inhibiting grazing effects on plant biomass and species richness. Mechanistically, fungal pathogens were linked to increased alkaloid and reduced nitrogen levels in leaf tissue, which appeared to deter cattle grazing on L. chinensis. In conclusion, foliar pathogens can suppress top-down effects of large herbivores on grassland community composition and ecosystem function by modifying the strength of their host's interactions with dominant consumers. Parasites may act as modulators of ecosystem function when their direct effects on host abundance are overshadowed by powerful influences on host traits that modify their interactions with competitors, herbivores, or predators.

Images of giant cell tumor and chondroblastoma around the knee: retrospective analysis of 99 cases.

Background: It is difficult to differentiate giant cell tumors of the bone (GCTB) from chondroblastoma around the knee based on imaging findings. This study analyzed the imaging features of these 2 diseases for better differentiation. Methods: This retrospective cross-sectional cohort study reviewed data of patients with pathologically confirmed GCTB (n=81; age 15-75 years; median age 33 years) and chondroblastoma (n=18; age 12-34 years; median age 14 years). In all, 18 imaging signs were analyzed. Results: Patients with chondroblastoma were relatively younger than those with GCTB. On imaging, lesion length was significantly (P<0.00001) smaller in chondroblastoma [range, 15.80-78.30 mm; mean ± standard deviation (SD) 34.15±18.24 mm; 95% confidence interval (CI): 24.05-44.25 mm] than in GCTB [range, 30.10-117.50 mm; mean ± SD 59.73±15.28 mm; 95% CI: 56.24-63.22 mm]. Significantly more (P<0.05) chondroblastoma lesions had calcification (76.5% vs. 1.3%), lobulation (77.8% vs. 32.1%), and swelling range >15 mm (84.6% vs. 41.1%) than did GCTB lesions, whereas significantly more (P<0.05) GCTB lesions were greater than half the host bone diameter (74.1% vs. 16.7%) and had a lesion long axis that was consistent with that of the host bone (98.8% vs. 27.8%). There were no significant differences (P>0.05) between the 2 tumors in the remaining 11 imaging signs. Conclusions: A narrow zone of transition, intratumor calcification, lobulation, tumor transverse diameter greater than the bone diameter, maximum lesion length, consistency between the tumor and bone long axes, and edema range around the lesion >15 mm are parameters that can be used to differentiate GCTB from chondroblastoma around the knee.

A novel adaptive cubic quasi-Newton optimizer for deep learning based medical image analysis tasks, validated on detection of COVID-19 and segmentation for COVID-19 lung infection, liver tumor, and optic disc/cup.

BACKGROUND: Most of existing deep learning research in medical image analysis is focused on networks with stronger performance. These networks have achieved success, while their architectures are complex and even contain massive parameters ranging from thousands to millions in numbers. The nature of high dimension and nonconvex makes it easy to train a suboptimal model through the popular stochastic first-order optimizers, which only use gradient information. PURPOSE: Our purpose is to design an adaptive cubic quasi-Newton optimizer, which could help to escape from suboptimal solution and improve the performance of deep neural networks on four medical image analysis tasks including: detection of COVID-19, COVID-19 lung infection segmentation, liver tumor segmentation, optic disc/cup segmentation. METHODS: In this work, we introduce a novel adaptive cubic quasi-Newton optimizer with high-order moment (termed ACQN-H) for medical image analysis. The optimizer dynamically captures the curvature of the loss function by diagonally approximated Hessian and the norm of difference between previous two estimates, which helps to escape from saddle points more efficiently. In addition, to reduce the variance introduced by the stochastic nature of the problem, ACQN-H hires high-order moment through exponential moving average on iteratively calculated approximated Hessian matrix. Extensive experiments are performed to access the performance of ACQN-H. These include detection of COVID-19 using COVID-Net on dataset COVID-chestxray, which contains 16 565 training samples and 1841 test samples; COVID-19 lung infection segmentation using Inf-Net on COVID-CT, which contains 45, 5, and 5 computer tomography (CT) images for training, validation, and testing, respectively; liver tumor segmentation using ResUNet on LiTS2017, which consists of 50 622 abdominal scan images for training and 26 608 images for testing; optic disc/cup segmentation using MRNet on RIGA, which has 655 color fundus images for training and 95 for testing. The results are compared with commonly used stochastic first-order optimizers such as Adam, SGD, and AdaBound, and recently proposed stochastic quasi-Newton optimizer Apollo. In task detection of COVID-19, we use classification accuracy as the evaluation metric. For the other three medical image segmentation tasks, seven commonly used evaluation metrics are utilized, that is, Dice, structure measure, enhanced-alignment measure (EM), mean absolute error (MAE), intersection over union (IoU), true positive rate (TPR), and true negative rate. RESULTS: Experiments on four tasks show that ACQN-H achieves improvements over other stochastic optimizers: (1) comparing with AdaBound, ACQN-H achieves 0.49%, 0.11%, and 0.70% higher accuracy on the COVID-chestxray dataset using network COVID-Net with VGG16, ResNet50 and DenseNet121 as backbones, respectively; (2) ACQN-H has the best scores in terms of evaluation metrics Dice, TPR, EM, and MAE on COVID-CT dataset using network Inf-Net. Particularly, ACQN-H achieves 1.0% better Dice as compared to Apollo; (3) ACQN-H achieves the best results on LiTS2017 dataset using network ResUNet, and outperforms Adam in terms of Dice by 2.3%; (4) ACQN-H improves the performance of network MRNet on RIGA dataset, and achieves 0.5% and 1.0% better scores on cup segmentation for Dice and IoU, respectively, compared with SGD. We also present fivefold validation results of four tasks. It can be found that the results on detection of COVID-19, liver tumor segmentation and optic disc/cup segmentation can achieve high performance with low variance. For COVID-19 lung infection segmentation, the variance on test set is much larger than on validation set, which may due to small size of dataset. CONCLUSIONS: The proposed optimizer ACQN-H has been validated on four medical image analysis tasks including: detection of COVID-19 using COVID-Net on COVID-chestxray, COVID-19 lung infection segmentation using Inf-Net on COVID-CT, liver tumor segmentation using ResUNet on LiTS2017, optic disc/cup segmentation using MRNet on RIGA. Experiments show that ACQN-H can achieve some performance improvement. Moreover, the work is expected to boost the performance of existing deep learning networks in medical image analysis.

Metabolism and residue differences of Enrofloxacin between the brain and peripheral tissues and the resulting brain damages in crucian carp (Carassius auratus var. Pengze).

This study aimed to explore the metabolism and residue differences of Enrofloxacin (ENR) at two doses between the brain and peripheral tissues (liver, kidney, and muscle) along with the brain damages caused by ENR in crucian carp (Carassius auratus var. Pengze). The concentrations of ENR in tissues were determined using a validated high-performance liquid chromatography (HPLC) analysis. Relying on the hematoxylin-eosin (HE) staining method, brain damages caused by the drug were evaluated by the section of pathological tissue. Metabolism and residue results showed that ENR could be detected in the brain throughout the experiment both at median lethal dose (LD50 at 96 h, 1949.84 mg/kg) and safe dose (SD, 194.98 mg/kg), as well as in the three peripheral tissues. The maximum residue at LD50 followed the decreasing order of liver >kidney > brain > muscle. Although the Cmax of ENR at SD in the brain was significantly lower than that in other peripheral tissues (p < .05), it still reached 41.91 µg/g. The T1/2 of ENR in brain tissue at the same dose was both shorter than that in peripheral tissues. At LD50 , the amount of ENR residues in brain was lower than that in peripheral tissues on the whole, except that it had been higher than in the muscle for the first 3 h. At SD, the drug residue in brain tissue was lower than that in peripheral tissues from 12 h to 960 h, but it exceeded the muscle and kidney at 1 h and 6 h, respectively. At 960 h, the residual amount of ENR at SD in the brain was 0.09 µg/g, while it was up to 0.15 µg/g following the oral administration at LD50 . Demonstrated by the HE staining, there were pathological lesions caused by ENR in the brain at LD50 , which were characterized by sparse neural network and increased staining of glial cells. The present results indicated that metabolism and residue of ENR in crucian carp were affected by the tissue type and drug dosage, and the ENR could also bring about histopathological changes in the brain.

Enhanced Catalytic Soot Oxidation over Co-Based Metal Oxides: Effects of Transition Metal Doping.

A series of Co-M (M = Fe, Cr, and Mn) catalysts were synthesized by the sol-gel method for soot oxidation in a loose contact mode. The Co-Fe catalyst exhibited the best catalytic activity among the tested samples, with the characteristic temperatures (T10, T50, and T90) of 470 °C, 557 °C, and 602 °C, respectively, which were 57 °C, 51 °C, and 51 °C lower than those of the CoOx catalyst. Catalyst characterizations of N2 adsorption-desorption, X-ray diffraction (XRD), X-ray photo-electron spectrometry (XPS), and the temperature programmed desorption of O2 (O2-TPD) were performed to gain insights into the relationships between the activity of catalytic soot oxidation and the catalyst properties. The content of Co2+ (68.6%) increased due to the interactions between Co and Fe, while the redox properties and the relative concentration of surface oxygen adsorption (51.7%) were all improved, which could significantly boost the activity of catalytic soot oxidation. The effects of NO and contact mode on soot oxidation were investigated over the Co-Fe catalyst. The addition of 1000 ppm of NO led to significant reductions in T10, T50, and T90 by 92 °C, 106 °C, and 104 °C, respectively, compared to the case without the NO addition. In the tight contact mode, the soot oxidation was accelerated over the Co-Fe catalyst, resulting in 46 °C, 50 °C, and 50 °C reductions in T10, T50, and T90 compared to the loose contact mode. The comparison between real soot and model Printex-U showed that the T50 value of real soot (455 °C) was 102 °C lower than the model Printex-U soot.