CRISETR: an efficient technology for multiplexed refactoring of biosynthetic gene clusters.

The efficient refactoring of natural product biosynthetic gene clusters (BGCs) for activating silent BGCs is a central challenge for the discovery of new bioactive natural products. Herein, we have developed a simple and robust CRISETR (CRISPR/Cas9 and RecET-mediated Refactoring) technique, combining clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 and RecET, for the multiplexed refactoring of natural product BGCs. By this approach, natural product BGCs can be refactored through the synergistic interaction between RecET-mediated efficient homologous recombination and the CRISPR/Cas9 system. We first performed a proof-of-concept validation of the ability of CRISETR, and CRISETR can achieve simultaneous replacement of four promoter sites and marker-free replacement of single promoter site in natural product BGCs. Subsequently, we applied CRISETR to the promoter engineering of the 74-kb daptomycin BGC containing a large number of direct repeat sequences for enhancing the heterologous production of daptomycin. We used combinatorial design to build multiple refactored daptomycin BGCs with diverse combinations of promoters different in transcriptional strengths, and the yield of daptomycin was improved 20.4-fold in heterologous host Streptomyces coelicolor A3(2). In general, CRISETR exhibits enhanced tolerance to repetitive sequences within gene clusters, enabling efficient refactoring of diverse and complex BGCs, which would greatly accelerate discovery of novel bioactive metabolites present in microorganism.

Efficient Adsorption and Degradation of Tetracycline Hydrochloride Using Metal-Organic Framework-Derived Cobalt-Based Catalysts and Mechanism Insight.

High-performance Co-based catalysts were derived by pyrolysis using synthesized MOFs as self-sacrificial templates. Various catalytic systems were constructed by peroxymonosulfate (PMS) to degrade tetracycline hydrochloride (TC). Adsorption-degradation efficiencies, cycle performance, dynamics, and the adsorption catalytic mechanism of various catalytic systems for TC were studied. The effects of different synthetic solvents, pyrolysis temperatures, and single/bimetallic element compositions on degradation efficiency were innovatively compared. The optimal catalyst and PMS dosage for the experiment were determined to be 10 mg and 0.1 mL, respectively. The results indicated that all catalytic systems could efficiently degrade TC and have a high acid-base resistance. The catalyst activity was significantly influenced by the pyrolysis temperature. The optimum pyrolysis temperatures for Zn@Co-N-C-T, CH3OH@Co-N-C-T, and H2O@Co-N-C-T were 1000, 900 and 900 °C, respectively. More abundant pore structures and active sites were generated in Zn@Co-N-C-1000, exhibiting an excellent TC degradation efficiency and adsorption capacity, achieving 94.73% and 167.564 mg/g, respectively. Meanwhile, the total organic carbon (TOC) of TC (50 mL, 50 mg/L) achieved a removal rate (TOC/TOC0) of 50.28%. Zn@Co-N-C-1000/PMS maintained over 83.27% TC degradation after five cycles. The adsorption mechanism of the catalyst for TC was investigated through the analysis of adsorption kinetics and isotherm models. The quenching test and EPR results indicated that TC was primarily degraded through the nonradical pathway. The efficient degradation of TC is attributed to the rapid electron transfer processes occurring at the two-phase interface and the redox cycling of Co0/Co2+/Co3+. Finally, LC-MS was used to analyze the intermediate products of TC degradation in the Zn@Co-N-C-1000/PMS system, and two degradation pathways were proposed.

Design of Fluxgate Current Sensor Based on Magnetization Residence Times and Neural Networks.

This study introduces a novel fluxgate current sensor with a compact, ring-shaped configuration that exhibits improved performance through the integration of magnetization residence times and neural networks. The sensor distinguishes itself with a unique magnetization profile, denoted as M waves, which emerge from the interaction between the target signal and ambient magnetic interference, effectively enhancing interference suppression. These M waves highlight the non-linear coupling between the magnetic field and magnetization residence times. Detection of these residence times is accomplished using full-wave rectification circuits and a Schmitt trigger, with a digital output provided by timing sequence detection. A dual-layer feedforward neural network deciphers the target signal, exploiting this non-linear relationship. The sensor achieves a linearity error of 0.054% within a measurement range of 15 A. When juxtaposed with conventional sensors utilizing the residence-time difference strategy, our sensor reduces linearity error by more than 40-fold and extends the effective measurement range by 150%. Furthermore, it demonstrates a significant decrease in ambient magnetic interference.

Fam20c regulates the calpain proteolysis system through phosphorylating Calpasatatin to maintain cell homeostasis.

BACKGROUND: The family with sequence similarity 20-member C (FAM20C) kinase, a Golgi casein kinase, which is responsible for phosphorylating the majority of the extracellular phosphoproteins within S-x-E/pS motifs, and is fundamentally associated with multiple biological processes to maintain cell proliferation, biomineralization, migration, adhesion, and phosphate homeostasis. In dissecting how FAM20C regulates downstream molecules and potential mechanisms, however, there are multiple target molecules of FAM20C, particularly many phenomena remain elusive, such as changes in cell-autonomous behaviors, incompatibility in genotypes and phenotypes, and others. METHODS: Here, assay for transposase-accessible chromatin using sequencing (ATAC-seq), RNA sequencing (RNA-seq), proteomics, and phosphoproteomics were performed in Fam20c-dificient osteoblasts and to facilitate an integrated analysis and determine the impact of chromatin accessibility, genomic expression, protein alterations, signaling pathway, and post translational modifcations. RESULTS: By combining ATAC-seq and RNA-seq, we identified TCF4 and Wnt signaling pathway as the key regulators in Fam20c-dificient cells. Further, we showed Calpastatin/Calpain proteolysis system as a novel target axis for FAM20C to regulate cell migration and F-actin cytoskeleton by integrated analysis of proteomics and phosphoproteomics. Furthermore, Calpastatin/Calpain proteolysis system could negatively regulate the Wnt signaling pathway. CONCLUSION: These observations implied that Fam20c knockout osteoblasts would cause cell homeostatic imbalance, involving changes in multiple signaling pathways in the conduction system.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data. / 基于GWASæ•°æ®åˆ†æžè‚ é“èŒç¾¤ä¸Žè„‘å‡ºè¡€çš„å ³ç³».

OBJECTIVES: Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms. METHODS: Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants. RESULTS: MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH. CONCLUSIONS: There is a causal association and pleiotropic variants between GM and ICH.

Downregulated Expression of RIPOR3 Correlated with Immune Infiltrates Predicts Poor Prognosis in Oral Tongue Cancer.

BACKGROUND Tongue cancer is the most prevalent of head and neck squamous cell carcinomas, including base of tongue cancer (BOT) and oral squamous cell carcinoma of the mobile tongue (OTSCC). We aimed to investigate the role of RIPOR3 in tumorigenesis and its development as a potential prognostic biomarker for tongue cancer, especially OTSCC. MATERIAL AND METHODS Associations of expression, clinical pathologic features, and overall survival were analyzed by logistic regression, multivariate Cox analysis, and Kaplan-Meier methods. Gene set enrichment analysis (GSEA) and the CIBERSORT algorithm were performed to determine the correlation between RIPOR3 and tumor immune infiltration. cBioPortal was used for methylation and copy number variation (CNV) analysis. The Human Protein Atlas (HPA) and GSE31056 dataset were used for further external validation. RESULTS RIPOR3 expression in OTSCC was significantly associated with various clinicopathological parameters. Kaplan-Meier survival analysis showed that OTSCC with low RIPOR3 expression had a worse prognosis than that with high RIPOR3 expression. Multivariate analysis revealed that lower RIPOR3 expression was an independent prognostic factor for poor prognosis. GSEA and Neighbor Gene Network analysis showed RIPOR3 expression was related with the modulation and function of the immune-related pathway. Methylation level and CNV analysis showed that the downregulated expression of RIPOR3 was significantly related to hypermethylation but not to CNV. Finally, high RIPOR3 expression was validated at the protein level using the HPA database and GSE31056 dataset. CONCLUSIONS These findings suggested that RIPOR3 might serve as a promising prognostic biomarker and is related to the immune cell infiltration of OTSCC.

Removal of sulfadiazine from aqueous solution by in-situ activated biochar derived from cotton shell.

Phosphoric acid is used to in-situ activate biochar pyrolyzed by cotton shells to enhance the adsorption ability of sulfadiazine (SDZ). To confirm the optimum condition, different impregnation ratios and impregnation times were investigated. It was found that the biochar (BC) pyrolyzed under the condition of an impregnation ratio of 2.5 and an impregnation time of 6 h showed the highest performance for the removal of SDZ. The maximum adsorption ability was 86.89 mg/g at a temperature of 298 K. The pseudo-second-order model was used to disclose the adsorption process of SDZ by BCs. The experimental data were described by the Langmuir and Temkin isotherms at different temperatures. It was found that the sorption of SDZ was an exothermic process according to the thermomechanical analysis. The activated BC could be recycled for at least five times with a high removal rate of SDZ. Thus, activated BCs are regarded as promising adsorbents for SDZ removal.

Effects of resveratrol on reducing spermatogenic dysfunction caused by high-intensity exercise.

BACKGROUND: Long-term high-intensity exercise can lead to reproductive endocrine and spermatogenic dysfunction. This research is to investigate the effect of resveratrol on the reduction of reproductive dysfunction induced by high-intensity exercise, and to screen relevant factors and signal transduction pathways. METHODS: Rats were randomly divided into three groups, a control group, an intensive exercise group (IE group), and a resveratrol-treated group (RSV group). After 9 weeks of exercise, the sperm density and reproductive hormone concentrations were measured, along with antioxidation, inflammatory cytokine production, and histological analyses performed for each group. In addition, a proteomics analysis of the IE group and RSV group were conducted. RESULTS: We found that compared with the control group, the average sperm density (P < 0.05) and testosterone concentration (P < 0.05) in the IE group decreased significantly. Additionally, in testis tissue the concentration of the inflammatory cytokines IL-6 (P < 0.01) and TNF-α (P < 0.01) increased significantly. Also, a significant decrease in superoxide dismutase (SOD) activity (P < 0.01) and a significant increase in the malondialdehyde (MDA) concentration (P < 0.01) were noted. In the RSV group, the average sperm density (P < 0.01), testosterone (P < 0.01) and follicle stimulating hormone (FSH) levels (P < 0.01) all increased in comparison to the IE group, and the concentration of IL-6 (P < 0.01) and TNF-α (P < 0.01) were found to be significantly decreased. Compared with the IE group, the SOD activity in the RSV group was significantly increased (P < 0.01), while the MDA content decreased (P < 0.01). Furthermore, histological analysis showed that the number of spermatogenic epithelial cells in the RSV group was higher than that of the IE group. There were a number of spermatogenic regulatory proteins identified in the proteomics analysis, including Clusterin, Piwi like homolog 1 (Piwil1), Zona pellucida binding protein (Zpbp), Heat shock-related 70 kDa protein 2 (Hspa2), Centrin 1, and Bardet-Biedl syndrome 2 protein (Bbs2). It was found that the proteins that differed between the two groups were mainly involved in pathways such as complement and coagulation cascades, the extracellular matrix-receptor interactions, etc. CONCLUSIONS: The present study demonstrates that after high-intensity exercise, the inflammatory cascade in the tissue of the testis increases with decreased resistance to oxidation and disordered spermatogenic function. Resveratrol can improve the reproductive dysfunction of rats that was induced by high-intensity exercise. It mostly promotes reproductive function by increasing testosterone secretion, reducing the inflammatory response, improving the antioxidant capacity, affecting the expression of spermatogenic regulatory proteins, and enhancing the signal transduction pathway of spermatogenesis.

Reflectance confocal microscopy and histological features of depigmentation after local corticosteroid injection.

BACKGROUND: Clinically, depigmentation after local corticosteroid injection is not rare. But there are less articles about its reflectance confocal microscopy (RCM) and histological features. This study aimed to define the RCM features and histopathologic findings of hypopigmentation after local corticosteroid injection and to analyze the correlations between the above two methods. METHODS: Forty cases with hypopigmentation after local corticosteroid injection were used to analyze the clinical and RCM features. Subsequently, for 20 of 40, an excision biopsy of the same imaged areas for histopathologic examination was executed. RESULTS: Our results showed that all 40 cases had round or ellipse hypopigmented macules with obscure boundary and 26 of 40 lesions' long diameter went along limbs. The RCM features and the histological findings revealed all patients had variable degrees of epidermal thinning, flattening rete ridges, reduced melanin, and no inflammatory cell infiltration. MART-1 analysis revealed the number of melanocytes was normal but with no or less melanin by Fontana-Masson staining. CONCLUSIONS: Depigmentation after local corticosteroid injection was a kind of disease with intact melanocytes, whose function was impaired. RCM features offer a high consistency with histopathologic findings. It thus constitutes a promising adjuvant tool for its diagnosis and for therapeutic follow-up.

Neurotoxic ß-amyloid oligomers cause mitochondrial dysfunction-the trigger for PANoptosis in neurons.

As the global population ages, the incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that ß-amyloid protein (Aß) deposition is a key factor leading to AD. However, the clinical efficacy of treating AD with anti-Aß protein antibodies is not satisfactory, suggesting that Aß amyloidosis may be a pathological change rather than a key factor leading to AD. Identification of the causes of AD and development of corresponding prevention and treatment strategies is an important goal of current research. Following the discovery of soluble oligomeric forms of Aß (AßO) in 1998, scientists began to focus on the neurotoxicity of AßOs. As an endogenous neurotoxin, the active growth of AßOs can lead to neuronal death, which is believed to occur before plaque formation, suggesting that AßOs are the key factors leading to AD. PANoptosis, a newly proposed concept of cell death that includes known modes of pyroptosis, apoptosis, and necroptosis, is a form of cell death regulated by the PANoptosome complex. Neuronal survival depends on proper mitochondrial function. Under conditions of AßO interference, mitochondrial dysfunction occurs, releasing lethal contents as potential upstream effectors of the PANoptosome. Considering the critical role of neurons in cognitive function and the development of AD as well as the regulatory role of mitochondrial function in neuronal survival, investigation of the potential mechanisms leading to neuronal PANoptosis is crucial. This review describes the disruption of neuronal mitochondrial function by AßOs and elucidates how AßOs may activate neuronal PANoptosis by causing mitochondrial dysfunction during the development of AD, providing guidance for the development of targeted neuronal treatment strategies.

Antibiotics daptomycin interacts with S protein of SARS-CoV-2 to promote cell invasion of Omicron (B1.1.529) pseudovirus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed enormous challenges to global public health. The use of antibiotics has greatly increased during the SARS-CoV-2 epidemic owing to the presence of bacterial co-infection and secondary bacterial infections. The antibiotics daptomycin (DAP) is widely used in the treatment of infectious diseases caused by gram-positive bacteria owing to its highly efficient antibacterial activity. It is pivotal to study the antibiotics usage options for patients of coronavirus infectious disease (COVID-19) with pneumonia those need admission to receive antibiotics treatment for bacterial co-infection in managing COVID-19 disease. Herein, we have revealed the interactions of DAP with the S protein of SARS-CoV-2 and the variant Omicron (B1.1.529) using the molecular docking approach and Omicron (B1.1.529) pseudovirus (PsV) mimic invasion. Molecular docking analysis shows that DAP has a certain degree of binding ability to the S protein of SARS-CoV-2 and several derived virus variants, and co-incubation of 1-100 µM DAP with cells promotes the entry of the PsV into human angiotensin-converting enzyme 2 (hACE2)-expressing HEK-293T cells (HEK-293T-hACE2), and this effect is related to the concentration of extracellular calcium ions (Ca2+). The PsV invasion rate in the HEK-293T-hACE2 cells concurrently with DAP incubation was 1.7 times of PsV infection alone. In general, our findings demonstrate that DAP promotes the infection of PsV into cells, which provides certain reference of antibiotics selection and usage optimization for clinicians to treat bacterial coinfection or secondary infection during SARS-CoV-2 infection.

Prokaryotic Expression and Affinity Purification of DDX3 Protein.

BACKGROUND: DDX3 is a protein with RNA helicase activity that is involved in a variety of biological processes, and it is an important protein target for the development of broad-spectrum antiviral drugs, multiple cancers and chronic inflammation. OBJECTIVES: The objective of this study is to establish a simple and efficient method to express and purify DDX3 protein in E. coli, and the recombinant DDX3 should maintain helicase activity for further tailor-made screening and biochemical function validation. METHODS: DDX3 cDNA was simultaneously cloned into pET28a-TEV and pNIC28-Bsa4 vectors and transfected into E. coli BL21 (DE3) to compare one suitable prokaryotic expression system. The 6×His-tag was fused to the C-terminus of DDX3 to form a His-tagging DDX3 fusion protein for subsequent purification. Protein dissolution buffer and purification washing conditions were optimized. The His-tagged DDX3 protein would bind with the Ni-NTA agarose by chelation and collected by affinity purification. The 6×His-tag fused with N-terminal DDX3 was eliminated from DDX3 by TEV digestion. A fine purification of DDX3 was performed by gel filtration chromatography. RESULTS: The recombinant plasmid pNIC28-DDX3, which contained a 6×His-tag and one TEV cleavage site at the N terminal of DDX3 sequence, was constructed for DDX3 prokaryotic expression and affinity purification based on considering the good solubility of the recombinant His-tagging DDX3, especially under 0.5 mM IPTG incubation at 18°C for 18 h to obtain more soluble DDX3 protein. Finally, the exogenous recombinant DDX3 protein was obtained with more than 95% purity by affinity purification on the Ni-NTA column and removal of miscellaneous through gel filtration chromatography. The finely-purified DDX3 still retained its ATPase activity. CONCLUSION: A prokaryotic expression pNIC28-DDX3 system is constructed for efficient expression and affinity purification of bioactive DDX3 protein in E. coli BL21(DE3), which provides an important high-throughput screening and validation of drugs targeting DDX3.

A 36-nW Electrocardiogram Anomaly Detector Based on a 1.5-bit Non-Feedback Delta Quantizer for Always-on Cardiac Monitoring.

An always-on electrocardiogram (ECG) anomaly detector (EAD) with ultra-low power (ULP) consumption is proposed for continuous cardiac monitoring applications. The detector is featured with a 1.5-bit non-feedback delta quantizer (DQ) based feature extractor, followed by a multiplier-less convolutional neural network (CNN) engine, which eliminates the traditional high-resolution analog-to-digital converter (ADC) in conventional signal processing systems. The DQ uses a computing-in-capacitor (CIC) subtractor to quantize the sample-to-sample difference of ECG signal into 1.5-bit ternary codes, which is insensitive to low-frequency baseline wandering. The subsequent event-driven classifier is composed of a low-complexity coarse detector and a systolic-array-based CNN engine for ECG anomaly detection. The DQ and the digital CNN are fabricated in 65-nm and 180-nm CMOS technology, respectively, and the two chips are integrated on board through wire bonding. The measured detection accuracy is 90.6% ∼ 91.3% when tested on the MIT-BIH arrhythmia database, identifying three different ECG anomalies. Operating at 1 V and 1.4 V power supplies for the DQ and the digital CNN, respectively, the measured long-term average power consumption of the core circuits is 36 nW, which makes the detector among those state-of-the-art always-on cardiac anomaly detection devices with the lowest power consumption.

DesTrans: A medical image fusion method based on Transformer and improved DenseNet.

Medical image fusion can provide doctors with more detailed data and thus improve the accuracy of disease diagnosis. In recent years, deep learning has been widely used in the field of medical image fusion. The traditional method of medical image fusion is to operate by superimposing and other methods of pixels. The introduction of deep learning methods has improved the effectiveness of medical image fusion. However, these methods still have problems such as edge blurring and information redundancy. In this paper, we propose a deep learning network model based on Transformer and an improved DenseNet network module integration that can be applied to medical images and solve the above problems. At the same time, the method can be moved to natural images. The use of Transformer and dense concatenation enhances the feature extraction capability of the method by limiting the feature loss which reduces the risk of edge blurring. We compared several representative traditional methods and more advanced deep learning methods with this method. The experimental results show that the Transformer and the improved DenseNet network module have a strong capability of feature extraction. The method yields good results both in terms of visual quality and objective image evaluation metrics.

Ozone degradation of tetracycline hydrochloride enhanced by magnetic nanofluid composed of Fe3O4 nanoparticles.

Magnetic Fe3O4 nanoparticles were added into the aqueous phase to form nanofluid systems, in which ozone was used for the oxidation of tetracycline hydrochloride (TC) in the solution. The nanomaterials were characterized using SEM, XRD, EDS, and FT-IR. The effects of nanoparticles size, addition ratio, and number of cycles on the process of ozone oxidation of TC were investigated. The results indicated that the addition ratio of nanoparticles have a certain impact on the performance of ozone oxidation. When the addition ratio increased from 0.02% to 0.4%, the removal rate of TC in the solution was improved significantly. Besides, the particle size of nanoparticles showed a greater impact on ozone oxidation. At the nanoscale, Fe3O4 nanoparticles exhibited significant strengthening properties, which is attributed to the construction of nanofluid systems. The removal rate of TC in solution decreased obviously with the increase of nanoparticles size. The Fe3O4 nanoparticles with particle size of 20 nm showed the most significant effect on TC degradation. The recycling experiment showed that magnetic Fe3O4 nanoparticles had stable regeneration performance. For three times of recycling treatment, with a Fe3O4 addition ratio of 0.4%, the removal rate of TC reached 98.7%, 97.21%, and 96%, respectively. Based on the characterization results, the strengthening mechanism was analyzed. The experimental results indicated that construction of nanofluids systems could improve the utilization rate of ozone, and Fe3O4 nanoparticles were reusable and easily recyclable.

Tethered Small-Molecule Acceptor Refines Hierarchical Morphology in Ternary Polymer Solar Cells: Enhanced Stability and 19% Efficiency.

Polymer solar cells (PSCs) are promising for efficient solar energy conversion, but achieving high efficiency and device longevity within a bulk-heterojunction (BHJ) structure remains a challenge. Traditional small-molecule acceptors (SMAs) in the BHJ blend show thermodynamic instability affecting the morphology. In contrast, tethered SMAs exhibit higher glass transition temperatures, mitigating these concerns. Yet, they might not integrate well with polymer donors, causing pronounced phase separation and overpurification of mixed domains. Herein, a novel ternary device is introduced that uses DY-P2EH, a tethered dimeric SMA with conjugated side-chains as host acceptor, and BTP-ec9, a monomeric SMA as secondary acceptor, which respectively possess hypomiscibility and hypermiscibility with the polymer donor PM6. This unique combination affords a parallel-connected ternary BHJ blend, leading to a hierarchical and stable morphology. The ternary device achieves a remarkable fill factor of 80.61% and an impressive power conversion efficiency of 19.09%. Furthermore, the ternary device exhibits exceptional stability, retaining over 85% of its initial efficiency even after enduring 1100 h of thermal stress at 85 °C. These findings highlight the potential advantage of tethered SMAs in the design of ternary devices with a refined hierarchical structure for more efficient and durable solar energy conversion technologies.

Knocking out FAM20C in pre-osteoblasts leads to up-regulation of osteoclast differentiation to affect long bone development.

Family with sequence similarity 20 member C (FAM20C) is a Golgi casein kinase that phosphorylates extracellularly-secreted regulatory proteins involved in bone development and mineralization, but its specific role in bone development is still largely unknown. In this study, to examine the specific mechanisms that FAM20C influences bone development, we cross-bred Osx-Cre with FAM20Cflox/flox mice to establish a Osx-Cre; FAM20Cflox/flox knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1-10 weeks, in which compared to control FAM20Cflox/flox, they had lower body weights and bone tissue mineralization. Furthermore, oKO had lower bone volume fractions, thickness, and trabecular numbers, along with higher degrees of trabecular separation. These mice also had decreased femoral metaphyseal cartilage proliferation layer, along with thickened hypertrophic layer and increased apoptotic cell counts. Transcriptomic analysis found that differentially-expressed genes in oKO were concentrated in the osteoclast differentiation pathway, in line with increased osteoclast presence. Additionally, up-regulation of osteoclast-related, and down-regulation of osteogenesis-related genes, were identified, in which the most up-regulated genes were signal regulatory protein ß-1 family (Sirpb1a-c) and mitogen-activated protein kinase 13. Overall, FAM20C KO in pre-osteoblasts leads to abnormal long bone development, likely due to subsequent up-regulation of osteoclast differentiation-associated genes.

Development of a nomogram-based model combining intra- and peritumoral ultrasound radiomics with clinical features for differentiating benign from malignant in Breast Imaging Reporting and Data System category 3-5 nodules.

Background: The differences in benign and malignant breast tumors are not only within the nodules but also involve changes in the surrounding tissues. Radiomics can reveal many details that are not discernible to the naked eye. This study aimed to distinguish between benign and malignant breast nodules using an ultrasound-based intra- and peritumoral radiomics model. Methods: This study retrospectively collected the information from 379 patients with Breast Imaging Reporting and Data System (BI-RADS) category 3-5 nodules and clear pathological diagnosis of breast nodules screened by routine ultrasound examination in the Sixth People's Hospital Affiliated to Medical College of Shanghai Jiao Tong University from January 2017 to December 2022. The largest dimension of the lesion on the 2D ultrasound image was selected to outline the area of interest which was conformally and outwardly expanded automatically by 5 mm to extract intra- and peritumor radiomics features. The included cases were randomly divided into training sets and test sets in a ratio of 7:3. The optimal features of the included models were retained by statistical and machine learning methods of dimensionality reduction, and logistic regression was used as the classifier to build an intratumoral model and a combined intratumoral-peritumoral radiomics model, respectively; through single-factor and multifactor logistic regression, the optimal features that could predict benign and malignant breast tumors were screened. The clinical and imaging models were established by selecting independent risk factors as clinical and imaging features through univariate and multifactorial logistic regression. Results: Among 379 BI-RADS category 3-5 breast nodules, there were 124 malignant nodules and 255 benign nodules; patients were aged 14 to 88 (46.22±15.51) years, and the age differences, radiomics score, and mass diameter between the training and test sets were not statistically significant (P>0.05). The intra- and peritumor radiomics model had an area under the curve (AUC) of 0.840 [95% confidence interval (CI): 0.766-0.914] in the test set. The model with intra- and peritumoral ultrasound radiomics features combined with clinical features had an AUC value of 0.960 (95% CI: 0.920-0.999). Conclusions: The nomogram, developed using intratumoral and peritumoral radiomics features combined with clinical risk features, demonstrated superior performance in distinguishing between benign and malignant BI-RADS 3-5 lesions.

HAKE: A Knowledge Engine Foundation for Human Activity Understanding.

Human activity understanding is of widespread interest in artificial intelligence and spans diverse applications like health care and behavior analysis. Although there have been advances with deep learning, it remains challenging. The object recognition-like solutions usually try to map pixels to semantics directly, but activity patterns are much different from object patterns, thus hindering another success. In this article, we propose a novel paradigm to reformulate this task in two-stage: first mapping pixels to an intermediate space spanned by atomic activity primitives, then programming detected primitives with interpretable logic rules to infer semantics. To afford a representative primitive space, we build a knowledge base including 26+ M primitive labels and logic rules from human priors or automatic discovering. Our framework, Human Activity Knowledge Engine (HAKE), exhibits superior generalization ability and performance upon canonical methods on challenging benchmarks. Code and data are available at http://hake-mvig.cn/.

Insight into the enhancement effect of amino functionalized carbon nanotubes on the H2S removal performance of nanofluid system.

By constructing nanofluid system, trace functionalized nanoparticles can significantly enhance the absorption performance of basic liquid. In this work, amino functionalized carbon nanotubes (ACNTs) and carbon nanotubes (CNTs) were introduced into alkaline deep eutectic solvents to build nanofluid systems and used for the dynamic absorption of H2S. The experiment results showed that the introduction of nanoparticles can significantly enhance the H2S removal performance of original liquid. When performing H2S removal experiments, the optimal mass concentrations of ACNTs versus CNTs were 0.05 % and 0.01 %, respectively. The characterization showed that the surface morphology and structure of the nanoparticles unchanged significantly during the absorption-regeneration process. A double mixed gradientless gas-liquid reactor was used to explore the gas-liquid absorption kinetics characteristics of the nanofluid system. It was found that the gas-liquid mass transfer rate increased significantly after the addition of nanoparticles. The highest total mass transfer coefficient of the nanofluid system of ACNTs was increased to more than 400 % of the value before the addition of nanoparticles. The analysis showed that the shuttle effect and hydrodynamic effect of nanoparticles play important role in the process of enhancing gas-liquid absorption, and the amino functionalization enhanced the shuttle effect of nanoparticles significantly.