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Abstract Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5–60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod—the simplest model of a nucleic acid—yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution.

Objectives: Artificial intelligence (AI) with white light imaging (WLI) is not enough for detecting non-polypoid colorectal polyps and it still has high false positive rate (FPR). We developed AIs using blue laser imaging (BLI) and linked color imaging (LCI) to detect them with specific learning sets (LS). Methods: The contents of LS were as follows, LS (WLI): 1991 WLI images of lesion of 2-10 mm, LS (IEE): 5920 WLI, BLI, and LCI images of non-polypoid and small lesions of 2-20 mm. LS (IEE) was extracted from videos and included both in-focus and out-of-focus images. We designed three AIs as follows: AI (WLI) finetuned by LS (WLI), AI (IEE) finetuned by LS (WLI)+LS (IEE), and AI (HQ) finetuned by LS (WLI)+LS (IEE) only with images in focus. Polyp detection using a test set of WLI, BLI, and LCI videos of 100 non-polypoid or non-reddish lesions of 2-20 mm and FPR using movies of 15 total colonoscopy were analyzed, compared to 2 experts and 2 trainees. Results: The sensitivity for LCI in AI (IEE) (83%) was compared to that for WLI in AI (IEE) (76%: p=0.02), WLI in AI (WLI) (57%: p

Abstract Radioiodine refractory (RAIR) patients do not benefit from iodine-131 therapy. Thus, timely identification of RAIR patients is critical for avoiding ineffective radioactive iodine therapy. In addition, determining the causes of iodine resistance will facilitate the development of novel treatment strategies. This study was comprised of 20 RAIR and 14 non-radioiodine refractory (non-RAIR) thyroid cancer patients. Liquid chromatography-mass spectrometry was used to identify differences in the serum metabolites of RAIR and non-RAIR patients. In addition, chemical assays were performed to determine the effects of the differential metabolites on iodine uptake. Metabolic pathway enrichment analysis of the differential metabolites revealed significant differences in the phenylalanine and tyrosine metabolic pathways. Notably, quinate and shikimic acid, metabolites of the tyrosine pathway, were significantly increased in the RAIR group. In contrast, the phenylalanine pathway metabolites, hippuric acid and 2-phenylacetamide, were markedly decreased in the RAIR group. Thyroid peroxidase plays an important role in catalyzing the iodination of tyrosine residues, while the ionic state of iodine promotes the iodination reaction. Quinate, shikimic acid, hippuric acid, and 2-phenylacetamide were found to be involved in the iodination of tyrosine, which is a key step in thyroid hormone synthesis. Specifically, quinate and shikimic acid were found to inhibit iodination, while hippuric acid and 2-phenylacetamide promoted iodination. Abnormalities in phenylalanine and tyrosine metabolic pathways are closely associated with iodine resistance. Tyrosine is required for thyroid hormone synthesis and could be a potential cause of iodine resistance.

Objectives: Detailed superiority of CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for polyp detection/diagnosis, compared to endoscopists is not well examined. We examined endoscopist's ability using movie sets of colorectal lesions which were detected and diagnosed by CAD EYE accurately. Methods: Consecutive lesions of 10 mm were examined live by CAD EYE from March-June 2022 in our institution. Short unique movie sets of each lesion with and without CAD EYE were recorded simultaneously using two recorders for detection under white light imaging (WLI) and linked color imaging (LCI) and diagnosis under blue laser/light imaging (BLI). Excluding inappropriate movies, 100 lesions detected and diagnosed with CAD EYE accurately were evaluated. Movies without CAD EYE were evaluated first by three trainees and three experts. Subsequently, movies with CAD EYE were examined. The rates of accurate detection and diagnosis were evaluated for both movie sets. Results: Among 100 lesions (mean size: 4.7±2.6 mm; 67 neoplastic/33 hyperplastic), mean accurate detection rates of movies without or with CAD EYE were 78.7%/96.7% under WLI (p

The study focuses on the critically endangered Dabry’s sturgeon (Acipenser dabryanus), a species on the brink of extinction in the wild. This research investigates the role of the Forkhead box protein L2 (foxl2) in the gonadal development and differentiation of this species. The foxl2 gene, known for its role in various physiological processes, including sexual maturation, is hypothesized to play a significant role in the sex differentiation of Dabry’s sturgeon. This study cloned the full-length cds sequence of the foxl2 gene and analyzed its expression across various tissues, focusing on its response to estradiol treatment. Our findings indicate that foxl2 is predominantly expressed in ovaries and shows a dose-dependent response to estradiol, suggesting its potential role in ovarian differentiation. This research underscores the importance of foxl2 in understanding reproductive biology and offers a foundation for future conservation strategies.

Cadmium (Cd) is a toxic heavy metal pollutant in the environment. Excessive Cd in water has toxic effects on fish, endangering their healthy growth and ultimately affecting the quality and safety of aquatic products. To evaluate the toxicity of excessive Cd to fish through potential oxidative damage, Siniperca chuatsi was exposed to Cd in water for 15 days. It was found that Cd exposure significantly decreased the survival rate of S. chuatsi and Cd was detected in their muscle. Meanwhile, Cd disrupts the redox balance by reducing antioxidant enzyme activities, increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle, and promoting oxidative damage. Histomorphology showed that enlargement of muscle fiber gaps, cell swelling and vacuolar degeneration after Cd exposure. In addition, Cd toxicity induced up-regulating the expression of miR-216a, while down-regulation of Nrf2 protein and its downstream antioxidant enzyme genes expression. Further analysis revealed that miR-216a was significantly negatively correlated with the expression of Nrf2, and injection of miR-216a antagomir significantly enhanced the expression of Nrf2 and antioxidant enzyme genes, as well as the activity of antioxidant enzymes, thereby reducing the damage of Cd to fish. These results suggested that miR-216a-mediated Nrf2 signaling pathway plays an important role in Cd-induced oxidative stress of S. chuatsi muscle.

BackgroundBiliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes.MethodologyThrough a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People’s Hospital affiliated with Jiangsu University and the Second People’s Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model’s accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model’s predictions.ResultsRF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor.ConclusionThe model’s effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

Abstract Chinese sturgeon Dmrt gene family was identified and characterized for the first time. A total of 5 putative Dmrt genes were identified. The gene structure, conserved protein domain and the phylogenetic relationship of Dmrt gene family were systematically analyzed. The expressed profile of Chinese sturgeon Dmrt genes in gonad, pituitary and hypothalamus in the male and female were investigated. The results indicated that the accumulation of Dmrt genes was involved in different tissues, and the expression profile also differed among each Dmrt genes. ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 were highly expressed in the testis in comparison with other tissue. This result showed that ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 played an important role in the development of testicle, and may be useful tool in distinguishing between male and female of Chinese sturgeon. Our study will provide a basis for additional analyses of Chinese sturgeon Dmrt genes. This systematic analysis provided a foundation for further functional characterization of Dmrt genes with an aim of study of Chinese sturgeon Dmrt gene family.

Abstract Background Gastric cancer at different locations has distinct prognoses and biological behaviors, but the specific mechanism is unclear. Methods Non-targeted metabolomics was performed to examine the differential metabolite phenotypes that may be associated with the effects of tumor location on the prognosis of gastric cancer. And silencing of the rate-limiting enzyme to evaluate the effect of abnormal changes in metabolic pathway on the functional biological assays of gastric cancer cells HGC-27 and MKN28. Results In a retrospective study of 94 gastric cancer patients, the average survival time of patients with gastric cancer in the middle third of the stomach was significantly lower than that of patients with gastric cancer in other locations (p

There is an interaction between subway station and the catchment area around the station, the catchment area of subway station on surrounding land is closely related to the connection modes. At present, subway passengers mainly reach subway stations by walking, cycling and bus, and the catchment area of the three connection modes is different. In order to clarify the catchment area of subway stations, it is necessary to study the catchment area of the three connection modes of subway stations. This study starts with a generalized connection cost for each connection mode, constructing the generalized connection cost models, especially considering the psychological changes of passengers with the increase of connecting distance. On this basis, we use Logit-SUE model to construct the probability density curve of the superior connection distance of different connection modes in different types and different area subway stations. Taking Beijing Metro Line 4 as the research case, through analyzing the probability density curve of each station of Line 4 we calculate the advantageous connection range of each subway station with different connection modes, and take the advantageous connection range as the catchment area for each type of connection mode.

Hepatitis C virus infection constitutes a significant global public health concern. Fluorescence technique (FL) is a promising biosensor, however, many conventional dyes exhibit reduced fluorescence or no emission at high concentrations. To break through this shackle, an ultrasensitive AIE-based (aggregation-induced emission) FL sensing platform was developed for HCV detection by using the FLRNAs-based T7 isothermal transcription amplification RNA diagnosis combined with AIE luminogens (FTAR) strategy. In the FTAR strategy, the T7 transcription amplification process was responsible for the recognition of the target HCV and produced Pepper aptamer, which could form aggregates of nanoparticles with the HBC, an AIEgen, to produce high-intensity FL. The multi-integrated signal amplification strategy led to ultrasensitivity. Moreover, under the optimal experimental conditions, HCV could be assayed in the range of 100aM-100pM. The proposed strategy has been successfully applied in detecting HCV in clinical samples. In summary, this research was the first to utilize aptamer restriction of AIEgens internal rotation to achieve aggregation-induced emission and presented the successful development of a specific, sensitive and rapid FTAR assay for HCV diagnosis. The proposed FTAR platform with facile operation, short analysis time, low-cost as well as excellent quantification ability could provide a promising tool for point-of-care testing (POCT).

Fatty acyl desaturases (Fads) are crucial enzymes that catalyze the rate-limiting step of the desaturation reactions by introducing a double bond into to pre-existing fatty acyl chains. As a group of key enzymes involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), Fads have been well investigated in teleost fishes but they are still rarely known in chondrichthyans. In this study, we first identified a fatty acyl desaturases gene (fads2) from the Chinese sturgeon (Acipenser sinensis), a critically endangered cartilaginous species in China, by combining with bioinformatic analyses and molecular cloning methods. Then, the spatio-temporal distribution patterns, functional characteristics and transcriptional changes of this gene in response to different nutritional conditions were investigated. The coding sequences of the fads2 gene was 1350 bp in length, encoding a protein of 449 amino acids. Multiple protein sequences alignment, genetic synteny and phylogenetic analyses further suggested that fads2 gene was evolutionary conserved. Functional characterization by heterologous expression in yeast showed that Fads2 exhibited Δ6 and Δ8 bifunctional desaturation activities, and possessed capacities to convert 18:2n-6, 18:3n-3, 20:2n-6 and 20:3n-3–18:3n-6, 18:4n-3, 20:3n-6 and 20:4n-3, respectively. In vivo experiment, diets full with C18 PUFA but not LC-PUFA significantly induced the expression levels of fads2 in Chinese sturgeon brain and liver tissues. Our findings suggest that fads2 is an evolutionary and functionally conserved desaturase in Chinese sturgeon, and which plays important roles in regulation of endogenous LC-PUFAs biosynthesis. In summary, these findings will provide a new insight into the evolutionary history of key enzymes of LC-PUFA biosynthesis in vertebrates.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment.

Summary: Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising chemotherapeutic drugs primarily against BRCA1/2-associated tumours, known as synthetic lethality. However, recent clinical trials reported patients’ survival benefits from PARP inhibitor treatments, irrelevant to homologous recombination deficiency. Therefore, revealing the therapeutic mechanism of PARP inhibitors beyond DNA damage repair is urgently needed, which can facilitate precision medicine. Methods: A CRISPR-based knock-in technology was used to establish stable BRCA1 mutant cancer cells. The effects of PARP inhibitors on BRCA1 mutant cancer cells were evaluated by biochemical and cell biological experiments. Finally, we validated its in vivo effects in xenograft and patient-derived xenograft (PDX) tumour mice. Findings: In this study, we uncovered that the majority of clinical BRCA1 mutations in breast cancers were in and near the middle of the gene, rather than in essential regions for DNA damage repair. Representative mutations such as R1085I and E1222Q caused transient extra spindle poles during mitosis in cancer cells. PAR, which is synthesized by PARP2 but not PARP1 at mitotic centrosomes, clustered these transient extra poles, independent of DNA damage response. Common PARP inhibitors could effectively suppress PARP2-synthesized PAR and induce cell senescence by abrogating the correction of mitotic extra-pole error. Interpretation: Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours. Funding: Funded by National Natural Science Foundation of China (NSFC) (T2225006, 82272948, 82103106), Beijing Municipal Natural Science Foundation (Key program Z220011), and the National Clinical Key Specialty Construction Program, P. R. China (2023).

Lipids are necessary nutrients for fish and play an important role in growth and metabolism. This study analyzed the effects of dietary lipid levels on growth performance, flesh quality, antioxidant status, and lipid metabolism of juvenile rice flower carp (Cyprinus carpio). The results showed that the weight gain rate and specific growth rate increased initially and then decreased with increasing dietary lipid levels, which 5.82 % dietary lipid level had the best growth in rice flower carp. Dietary lipid levels also affect the nutrition and quality of fish flesh. With the increase of dietary lipid levels, the hardness, adhesiveness, springiness, gumminess and chewiness of muscle showed a trend of increase and then decrease. Moreover, there are similar changes in the activity of antioxidant enzymes in the muscle, and the content of ROS and MDA was significantly higher than other levels at 11.80 % dietary lipid level. The expression of Nrf2 mRNA and some downstream antioxidant enzyme genes was the contrary. Furthermore, the content of TG, TC, and LDL-C in serum and liver increased with increasing dietary lipid levels. Meanwhile, it was observed that the lipid accumulation increased in the liver. The mRNA expression of ATGL and CPT1 genes associated with lipid metabolism in liver increased firstly and then decreased, the expression of FASN, PPARγ, and SREBP1 gradually increased, and reached its maximum at 11.8 % dietary lipid level. The above results showed that the growth performance of juvenile rice flower carp was optimal when the dietary lipid level of 5.82 %, and the nutrition and quality of fish flesh also has good effects. However, the dietary lipid level of 11.80 % inhibited the weight gain and induced oxidative stress and lipid metabolism disorders of rice flower carp, which can affect their flesh quality and health.

ABSTRACT: This study evaluated the impact of dietary digestible aromatic amino acid (DAAA) levels and stachyose on growth, nutrient utilization and cecal odorous compounds in broiler chickens. A 3×2 two-factor factorial design: Three dietary DAAA levels (1.40, 1.54, 1.68%) supplemented with either 5 g/kg of stachyose or without any stachyose were used to create 6 experimental diets. Each diet was fed to 6 replicates of 10 birds from d 22 to 42. Findings revealed that broilers receiving a diet with 1.54% DAAA levels supplemented with 5 g/kg stachyose exhibited a significant boost in average daily gain and improved utilization of crude protein, ether extract, tryptophan, and methionine compared to other diet treatments (P < 0.05). As the dietary DAAA levels increased, there was a significant rise in the concentrations of indole, skatole, p-methylphenol, and butyric acid in the cecum of broilers (P < 0.05). The addition of stachyose to diets reduced concentrations of indole, skatole, phenol, p-methylphenol, acetic acid and propionic acid in the cecum (P < 0.05). The lowest concentrations of indole, phenol, p-methylphenol, volatile fatty acids and pH in cecum of broilers were observed in the treatment which diet DAAA level was 1.40% with stachyose (P < 0.05). In conclusion, dietary DAAA levels and stachyose had significant interactions on the growth, main nutrient utilization and cecal odorous compounds in broilers. The dietary DAAA level was 1.54% with 5 g/kg of stachyose can improve the growth performance, nutrient utilization. However, the dietary DAAA level was 1.40% with stachyose was more beneficial to decrease the cecal odor compound composition in broilers.

Abstract The dimension of the void area in pavement is crucial to its structural safety. However, there is no effective method to measure its geometric parameters. To address this issue, a void size extraction algorithm based on the continuous wavelet transform (CWT) method was proposed using ground-penetrating radar (GPR) signal. Firstly, the finite-difference time-domain (FDTD) method was used to investigate the GPR response of void areas with different shapes, sizes, and depths. Next, the GPR signal was processed using the CWT method, and a 3D image based on the CWT result was used to visualize the void area. Based on the differences between the void and normal pavement in the time and frequency domains, the signal with maximum energy from the CWT time–frequency result was extracted and combined to reconstruct the new B-scan image, where void areas have energy concentration phenomenon. Based on this, width and depth of void detection algorithm was proposed to recognize the void area. Finally, the detection algorithm was verified both in numerical model and physical lab model. The results indicated that the CWT time–frequency energy spectrum can be used to enhance the void feature, and the 3D CWT image can clearly visualize the void area with a highlighted energy area. After fully testing and validating in numerical and lab models, our proposed method achieved high accuracy in void width and depth detection, providing a precise method for estimating void dimension in pavement. This method can guide DOT departments to carry out pre-maintenance, thereby ensuring pavement safety.

Objective The objective of this study was to investigate the effect of supplementation with enzymolytic soybean meal (ESBM) on broilers fed low crude protein (CP) diets. Methods A total of 360 one-day-old broilers were randomly assigned to six treatments with 6 replicates per treatment and 10 chicks per replicate for a period of 42 days. Chicks were fed a basal standard high-CP diet as a positive control (PC), a low-CP diet (reducing 10 g/kg CP from the PC) as a negative control (NC), or an NC + 0.5%, 1.0%, 1.5%, or 2.0% ESBM diet. Results Compared to chicks fed the PC, chicks fed the NC had a decreased body weight gain (BWG, p0.05) serum concentrations of total protein, albumin and total cholesterol but led to a descending trend in triglycerides and an ascending trend in calcium and urea N at 42 days (p0.05) in villus height (VH), crypt depth (CD), and VH/CD (V/C) of the duodenum and jejunum between the PC and NC at both 21 days and 42 days, while increasing dietary ESBM levels linearly (p

Elongases of very-long-chain fatty acids (Elovls) are critical rate-limiting enzymes that are involved in LC-PUFA biosynthesis through catalyzing the two-carbon elongation of a pre-existing fatty acyl chain. Thus far, several Elovls have been extensively studied in teleost. However, the functional and physiological roles of Elovls in chondrichthyans have rarely been reported. In this study, we identified and characterized elovl2 from the endangered Chinese sturgeon (Acipenser sinensis) by whole genome scanning. The results show that the coding sequence of elovl2 was 894 bp in length, for a putative protein of 297 amnio acids. Comparative genomic analyses indicated that Chinese sturgeon elovl2 was evolutionarily conserved. Functional characterization in yeast demonstrated that the Chinese sturgeon Elovl2 could efficiently elongate C20 (ARA and EPA) and C22 (22:4n-6 and 22:5n-3) substrates, confirming its critical roles in LC-PUFA biosynthesis. Spatial and temporal expression analyses showed high elovl2 mRNA levels were detected in the liver and brain and showed an increase trend both in embryonic and post-hatching stages. Interestingly, diets with vegetable oils as lipid sources could significantly induce the high expression of elovl2 in Chinese sturgeon, implying that the endogenous LC-PUFA biosynthesis pathway was stimulated by lack of LC-PUFA in their diets. Our findings will enhance our understanding about the evolutionary and functional roles of elovl2 and provide novel insights into the LC-PUFA biosynthesis mechanism in vertebrates.

Spatial–temporal variation in soil organic carbon is an important factor for national targets to mitigate climate change and land degradation impacts. In this research, we took Guangdong Province of China as the study area, evaluated the spatial–temporal distributions of soil organic carbon using data from three China Geochemical Baseline projects (conducted in 2009, 2016, and 2023, respectively), and quantified the main driving factors of spatial–temporal variations in soil organic carbon using the random forest algorithm, further predicting the density and inventories of soil organic carbon. The results demonstrate that the mean value of SOC in Guangdong in 2009 was 0.81%; in 2016 it was 1.13%; and in 2023 it was 1.02%. The inventories of soil organic carbon (0–30 cm) in Guangdong Province were 0.61 Pg in 2009, 0.74 Pg in 2016, and 0.62 Pg in 2023. Soil in Guangdong acted as a carbon sink from 2009 to 2023 as a whole, and the most important driving force behind spatial–temporal variations in soil organic carbon was temperature, followed by precipitation and vegetation cover.

We have designed a high-resolution magnetic field imaging system using 256 unpackaged Hall elements. These unpackaged Hall elements are arranged in a Hall linear array, and the distance between adjacent elements reaches 255 µm. The sensitivity of the unpackaged Hall element array can be adjusted using a computer to measure magnetic environments with different magnetic field strengths. High-resolution magnetic field images of 256 × 256 pixels can be generated by moving the array using the X–Y axis motorized rail. This spatial resolution can reach 99.61 pixels per inch (ppi). This rail allows for the spatial resolution of the system to be further increased to 199.22 ppi by using a special movement route. In the experiments, we employ this system to image magnetized metal scissors, and the result displays the structural features of the scissor surface. We also detected the magnetic suction wireless charging coil inside an Apple phone. The image obtained shows the shape of the coil and the gap between the magnets. The high-resolution magnetic imaging system displays the magnetic characteristics of the sample very well and easily obtains information about small-shaped structures and defects on the sample surface. This provides the system with potential in several fields such as quality inspection, security, biomedicine, and detection imaging.

Automated perimetrium segmentation of transvaginal ultrasound images is an important process for computer-aided diagnosis of uterine diseases. However, ultrasound images often contain various structures and textures, and these structures have different shapes, sizes, and contrasts; therefore, accurately segmenting the parametrium region of the uterus in transvaginal uterine ultrasound images is a challenge. Recently, many fully supervised deep learning-based methods have been proposed for the segmentation of transvaginal ultrasound images. Nevertheless, these methods require extensive pixel-level annotation by experienced sonographers. This procedure is expensive and time-consuming. In this paper, we present a bidirectional copy–paste Mamba (BCP-Mamba) semi-supervised model for segmenting the parametrium. The proposed model is based on a bidirectional copy–paste method and incorporates a U-shaped structure model with a visual state space (VSS) module instead of the traditional sampling method. A dataset comprising 1940 transvaginal ultrasound images from Tongji Hospital, Huazhong University of Science and Technology is utilized for training and evaluation. The proposed BCP-Mamba model undergoes comparative analysis with two widely recognized semi-supervised models, BCP-Net and U-Net, across various evaluation metrics including Dice, Jaccard, average surface distance (ASD), and Hausdorff_95. The results indicate the superior performance of the BCP-Mamba semi-supervised model, achieving a Dice coefficient of 86.55%, surpassing both U-Net (80.72%) and BCP-Net (84.63%) models. The Hausdorff_95 of the proposed method is 14.56. In comparison, the counterparts of U-Net and BCP-Net are 23.10 and 21.34, respectively. The experimental findings affirm the efficacy of the proposed semi-supervised learning approach in segmenting transvaginal uterine ultrasound images. The implementation of this model may alleviate the expert workload and facilitate more precise prediction and diagnosis of uterine-related conditions.

Background: Bladder cancer (BLCA) is a common malignant tumor of urinary system and prognostic biomarkers are needed for better clinical decision-making and patient management. Cancer stem cells (CSCs) are involved in carcinogenesis, development, metastasis and recurrence of BLCA. This study explored the prognostic and predictive value of CSCs-related genes and laid the groundwork for precision treatment development in BLCA. Methods: The mRNA data and corresponding clinical information obtained from TCGA-BLCA cohort was used to discover biomarkers and develop CSCs-related prognostic model, which was further validated in GSE32548 and GSE32894 datasets. In addition, the association between CSCs-related risk score and therapeutic efficacy was analyzed to explore the potential predictive value of the prognostic model. Results: We identified four CSCs-related subtypes and 900 differentially expressed genes (DEGs) among subtypes. Then the CSCs-related prognostic model was built based on 16 CSCs-related DEGs with the most significant prognostic value. Patients in the low-risk group had better overall survival than those in high-risk group (P

Abstract Silicic magmas are the most viscous of all magmas, however some granitic plutons display remarkably homogeneous compositions, which contradicts the hypothesis that mechanical mixing is the main homogenizing process in the magma chamber. Thus much remains controversial about the mechanisms responsible for the homogeneities of silicic plutons. Here, we present textural observations, elemental mapping, and in situ elemental and Nd‐O isotopic data of apatites from the compositionally homogeneous Late Permian Yuanyang A‐type granitic pluton (SW Yunnan, South China). Apatite grains display oscillatory chemical zonation and resorption‐precipitation texture, suggesting incremental growth dominated by co‐genetic magma batches injection. The intra‐/inter‐grain core to rim elemental and Nd‐O isotopic variations imply crystal transfer and crystallization from different melt domains within the crystal mush. We propose that rejuvenation events associated with hotter cogenetic intermediate magma batch injection has induced crystal mush reactivation and convective stirring in silicic magma chambers, thereby homogenizing the entire reservoir.

Summary: Despite autophagy modulating tumor immunity in the tumor microenvironment (TME), the immunotherapeutic efficacy and potential mechanism of autophagy signature was not explicit. We manually curated an autophagy gene set and defined a pan-cancer autophagy signature by comparing malignant tissues and normal tissues in The Cancer Genome Atlas (TCGA) cohort. The pan-cancer autophagy signature was derived from T proliferating cells as demonstrated in multiple single-cell RNA sequencing (scRNA-seq) datasets. The pan-cancer autophagy signature could influence the cell-cell interactions in the TME and predict the responsiveness of immune checkpoint inhibitors (ICIs) in the metastatic renal cell carcinoma, non-small cell lung cancer, bladder cancer, and melanoma cohorts. Metabolism inactivation accompanied with dysregulation of autophagy was investigated with transcriptomic and proteomic data. The immunotherapeutic predictive role and mechanism regulation of the autophagy signature was validated in an in-house cohort. Our study provides valuable insights into the mechanisms of ICI resistance.

Abstract Identifying the primary site of metastatic cancer is critical to guiding the subsequent treatment. Approximately 3–9% of metastatic patients are diagnosed with cancer of unknown primary sites (CUP) even after a comprehensive diagnostic workup. However, a widely accepted molecular test is still not available. Here, we report a method that applies formalin-fixed, paraffin-embedded tissues to construct reduced representation bisulfite sequencing libraries (FFPE-RRBS). We then generate and systematically evaluate 28 molecular classifiers, built on four DNA methylation scoring methods and seven machine learning approaches, using the RRBS library dataset of 498 fresh-frozen tumor tissues from primary cancer patients. Among these classifiers, the beta value-based linear support vector (BELIVE) performs the best, achieving overall accuracies of 81-93% for identifying the primary sites in 215 metastatic patients using top-k predictions (k = 1, 2, 3). Coincidentally, BELIVE also successfully predicts the tissue of origin in 81-93% of CUP patients (n = 68).

Abstract Background Public complaints concerning odor emissions from intensive livestock and poultry farms continue to grow, as nauseous odorous compounds have adverse impacts on the environment and human health. Itaconic acid is a metabolite from the citric acid cycle of the host and shows volatile odor-reducing effects during animal production operations. However, the specific role of itaconic acid in decreasing intestinal odorous compound production remains unclear. A total of 360 one-day-old chicks were randomly divided into 6 treatment groups: control group (basal diet) and itaconic acid groups (basal diet + 2, 4, 6, 8 and 10 g/kg itaconic acid). The feeding experiment lasted for 42 d. Results Dietary itaconic acid supplementation linearly and quadratically decreased (P < 0.05) the cecal concentrations of indole and skatole but did not affect (P > 0.05) those of lactic, acetic, propionic and butyric acids. The cecal microbial shift was significant in response to 6 g/kg itaconic acid supplementation, in that the abundances of Firmicutes, Ruminococcus and Clostridium were increased (P < 0.05), while those of Bacteroidetes, Escherichia-Shigella and Bacteroides were decreased (P < 0.05), indicative of increased microbial richness and diversity. Furthermore, a total of 35 significantly (P < 0.05) modified metabolites were obtained by metabolomic analysis. Itaconic acid decreased (P < 0.05) the levels of nicotinic acid, nicotinamide, glucose-6-phosphate, fumatic acid and malic acid and increased (P < 0.05) 5-methoxytroptomine, dodecanoic acid and stearic acid, which are connected with the glycolytic pathway, citrate acid cycle and tryptophan metabolism. Correlation analysis indicated significant correlations between the altered cecal microbiota and metabolites; Firmicutes, Ruminococcus and Clostridium were shown to be negatively correlated with indole and skatole production, while Bacteroidetes, Escherichia-Shigella and Bacteroides were positively correlated with indole and skatole production. Conclusions Itaconic acid decreased cecal indole and skatole levels and altered the microbiome and metabolome in favor of odorous compound reduction. These findings provide new insight into the role of itaconic acid and expand its application potential in broilers.

The precise mapping of magnetic fields emitted by various objects holds critical importance in the fabrication of industrial products. To meet this requirement, this study introduces an advanced magnetic detection device boasting high spatial resolution. The device’s sensor, an array comprising 256 unpackaged gallium arsenide (GaAs) Hall elements arranged in a 16 × 16 matrix, spans an effective area of 19.2 mm × 19.2 mm. The design maintains a 1.2 mm separation between adjacent elements. For enhanced resolution, the probe scans the sample via a motorized rail system capable of executing specialized movement patterns. A support structure incorporated into the probe minimizes the measurement distance to below 0.5 mm, thereby amplifying the magnetic signal and mitigating errors from nonparallel probe–sample alignment. The accompanying interactive software utilizes cubic spline interpolation to transform magnetic readings into detailed two- and three-dimensional magnetic field distribution maps, signifying field strength and polarity through variations in color intensity and amplitude sign. The device’s efficacy in accurately mapping surface magnetic field distributions of magnetic and magnetized materials was corroborated through tests on three distinct samples: a neodymium–iron–boron magnet, the circular magnetic array from a smartphone, and a magnetized 430 steel plate. These tests, focused on imaging quality and magnetic field characterization, underscore the device’s proficiency in nondestructive magnetic field analysis.

The study of extreme events (EEs) in photonics has expanded significantly due to straightforward implementation conditions. EEs have not been discussed systematically, to the best of our knowledge, in the chaotic dynamics of a Fabry–Perot laser with optical feedback, so we address this in the current contribution. Herein, we not only find EEs in all modes but also divide the EEs in total output into two categories for further discussion. The two types of EEs have similar statistical features to conventional rogue waves. The occurrence probability of EEs undergoes a saturation effect as the feedback strength increases. Additionally, we analyze the influence of feedback strength, feedback delay, and pump current on the probability of EEs defined by two criteria of EEs and find similar trends. We hope that this work contributes to a deep understanding and serves as inspiration for further research into various multimode semiconductor laser systems.

Abstract Quantum entanglement between an interfering particle and a detector for acquiring the which-path information plays a central role for enforcing Bohr’s complementarity principle. However, the quantitative relation between this entanglement and the fringe visibility remains untouched upon for an initial mixed state. Here we find an equality for quantifying this relation. Our equality characterizes how well the interference pattern can be preserved when an interfering particle, initially carrying a definite amount of coherence, is entangled, to a certain degree, with a which-path detector. This equality provides a connection between entanglement and interference in the unified framework of coherence, revealing the quantitative entanglement-interference complementarity. We experimentally demonstrate this relation with a superconducting circuit, where a resonator serves as a which-path detector for an interfering qubit. The measured fringe visibility of the qubit’s Ramsey signal and the qubit-resonator entanglement exhibit a complementary relation, in well agreement with the theoretical prediction.

BackgroundThe objective of this study was to explore the association between the sarcopenia index and abnormal liver function in adult individuals in the United States.MethodologyThis study employed a rigorous cross-sectional analysis of data derived from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018. The primary objective was to investigate the correlation between the sarcopenia index and abnormal liver function. To achieve this, an advanced multivariate regression model was utilized, allowing for comprehensive analysis and meticulous adjustment of relevant variables. To ensure the robustness of the findings, a visually appealing smooth curve was constructed, and a two-stage regression model was applied for validation. Additionally, a detailed gender-stratified analysis was conducted to further explore the association between the sarcopenia index and abnormal liver function within distinct subgroups.ResultsThrough our rigorous participant selection process, a total of 1756 individuals were included in the study. The meticulously adjusted multivariate regression model revealed a significant negative association between the sarcopenia index and abnormal liver function, with an adjusted odds ratio (OR) of 0.73 and a 95% confidence interval (CI) ranging from 0.63 to 0.86. The robustness of this association was further supported by the visually appealing smooth curve plot. Moreover, in the gender-stratified subgroup analysis, after meticulous adjustment for confounding factors, notable differences in this association emerged (males: OR = 0.8, 95% CI: 0.66–0.98; females: OR = 0.61, 95% CI: 0.47–0.79).ConclusionThis cross-sectional study yields robust evidence indicating a negative correlation between the sarcopenia index and abnormal liver function, predominantly observed among females.

The objective of this experiment was to determine the effect of low crude protein (CP) diets containing increasing amounts of enzymolytic soybean meal (ESBM) on growth performance, economic benefit and organ development and the role of cecal fermentation and microbiota in broilers. A total of 360 one-day-old Arbor Acres chicks were randomly allocated into 6 groups with 6 replicates and 10 chicks each. The six dietary treatments consisted of a standard high-CP diet (PC), a low-CP diet (NC), and an NC diet with 0.5, 1.0, 1.5%, or 2.0% ESBM. The experiment lasted for 42 days. Compared to PC, NC showed decreased (p 0.05), while the cecal abundances of Bacteroides, Faecalibacterium and Clostridium IV increased (p

Due to the complicated transport and reactive behavior of organic contamination in groundwater, the development of mathematical models to aid field remediation planning and implementation attracts increasing attentions. In this study, the approach coupling response surface methodology (RSM), artificial neural networks (ANN), and kinetic models was implemented to model the degradation effects of nano-zero-valent iron (nZVI) activated persulfate (PS) systems on benzene, a common organic pollutant in groundwater. The proposed model was applied to optimize the process parameters in order to help predict the effects of multiple factors on benzene degradation rate. Meanwhile, the chemical oxidation kinetics was developed based on batch experiments under the optimized reaction conditions to predict the temporal degradation of benzene. The results indicated that benzene (0.25 mmol) would be theoretically completely oxidized in 1.45 mM PS with the PS/nZVI molar ratio of 4:1 at pH 3.9°C and 21.9 C. The RSM model predicted well the effects of the four factors on benzene degradation rate (R2 = 0.948), and the ANN with a hidden layer structure of [8-8] performed better compared to the RSM (R2 = 0.980). In addition, the involved benzene degradation systems fit well with the Type-2 and Type-3 pseudo-second order (PSO) kinetic models with R2 > 0.999. It suggested that the proposed statistical and kinetic-based modeling approach is promising support for predicting the chemical oxidation performance of organic contaminants in groundwater under the influence of multiple factors.

Objective This study was conducted to evaluate the interactive effects of dietary digestible tryptophan (dTry) and soy oligosaccharides (SO) on growth performance, caecal skatole level, and microflora of broiler chickens aged from 14 to 42 days. Methods Three hundred and sixty broiler chicks were allocated equally to 36 cages at 14-day-of-age according to body weight and gender. Using a 3×2 factorial arrangement, 3 dietary dTry levels (0.18%, 0.23%, and 0.28%) supplemented with 0 or 3.5 g/kg of SO were used to create 6 diets (treatments). Each diet was fed to six replicates of 10 birds (60 birds/treatment), growth performance was measured. Caecal content samples were collected at 42 days of age. Results Results showed that significantly different dTry level×SO interactions were found for average daily gain (ADG), caecal levels of indole, propionic acid, and butyric acid, and microbial Shannon index (p

The Sustainable Sites Initiative (SITES) is a comprehensive evaluation system for sustainable landscape, which has been promoted successfully and widely recognized in the landscape architecture industry. However, the existing research lacks attention to the applicability of SITES to urban green space construction projects in China. Therefore, exploring the application of the SITES evaluation system in the context of Chinese urban green space development is of great importance. Building upon theoretical research on sustainable landscapes, this study focuses on urban green space projects as the research carrier, with SITES as the subject of investigation. Utilizing the case study method, a thorough description and analysis of Xuhui Runway Park, a representative case officially certified by SITES in China, is provided. Across four stages—project initiation and planning, scheme design, construction, and operation—this study discusses the approaches employed in Chinese urban green space projects to meet the requirements of the SITES evaluation system. By evaluating the applicability of SITES to Chinese urban green space projects, identifying limitations in system promotion, and offering references for sustainable design practices, this study advances the application and promotion of SITES in China and contributes to the sustainable development of the landscape architecture industry.

Physiology disorders of the liver, as it is an important tissue in lipid metabolism, can cause fatty liver disease. The mechanism might be regulated by 17 circadian clock genes and 18 fat metabolism genes, together with a high-fat diet (HFD). Due to their rich nutritional and medicinal value, Chinese soft-shelled turtles (Trionyx sinensis) are very popular among the Chinese people. In the study, we aimed to investigate the influence of an HFD on the daily expression of both the core clock genes and the lipid metabolism genes in the liver tissue of the turtles. The two diets were formulated with 7.98% lipid (the CON group) and 13.86% lipid (the HFD group) to feed 180 juvenile turtles, which were randomly divided into two groups with three replicates per group and 30 turtles in each replicate for six weeks, and the diet experiment was administrated with a photophase regimen of a 24 h light/dark (12L:12D) cycle. At the end of the experiment, the liver tissue samples were collected from nine turtles per group every 3 h (zeitgeber time: ZT 0, 3, 6, 9, 12, 15, 18, 21 and 24) for 24 h to investigate the daily expression and correlation analysis of these genes. The results showed that 11 core clock genes [i.e., circadian locomotor output cycles kaput (Clock), brain and muscle arnt-like protein 1 and 2 (Bmal1/2), timeless (Tim), cryptochrome 1 (Cry2), period2 (Per2), nuclear factor IL-3 gene (Nfil3), nuclear receptor subfamily 1, treatment D, member 1 and 2 (Nr1d1/2) and retinoic acid related orphan receptor α/β/γ β and γ (Rorβ/γ)] exhibited circadian oscillation, but 6 genes did not, including neuronal PAS domain protein 2 (Npas2), Per1, Cry1, basic helix-loop-helix family, member E40 (Bhlhe40), Rorα and D-binding protein (Dbp), and 16 lipid metabolism genes including fatty acid synthase (Fas), diacylglycerol acyltransferase 1 (Dgat1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), Low-density lipoprotein receptor-related protein 1-like (Ldlr1), Lipin 1 (Lipin1), Carnitine palmitoyltransferase 1A (Cpt1a), Peroxisome proliferator activation receptor α, β and γ (Pparα/β/γ), Sirtuin 1 (Sirt1), Apoa (Apoa1), Apolipoprotein B (Apob), Pyruvate Dehydrogenase kinase 4 (Pdk4), Acyl-CoA synthase long-chain1 (Acsl1), Liver X receptors α (Lxrα) and Retinoid X receptor, α (Rxra) also demonstrated circadian oscillations, but 2 genes did not, Scd and Acaca, in the liver tissues of the CON group. However, in the HFD group, the circadian rhythms’ expressional patterns were disrupted for the eight core clock genes, Clock, Cry2, Per2, Nfil3, Nr1d1/2 and Rorβ/γ, and the peak expression of Bmal1/2 and Tim showed delayed or advanced phases. Furthermore, four genes (Cry1, Per1, Dbp and Rorα) displayed no diurnal rhythm in the CON group; instead, significant circadian rhythms appeared in the HFD group. Meanwhile, the HFD disrupted the circadian rhythm expressions of seven fat metabolism genes (Fas, Cpt1a, Sirt1, Apoa1, Apob, Pdk4 and Acsl1). Meanwhile, the other nine genes in the HFD group also showed advanced or delayed expression peaks compared to the CON group. Most importantly of all, there were remarkably positive or negative correlations between the core clock genes and the lipid metabolism genes, and their correlation relationships were altered by the HFD. To sum up, circadian rhythm alterations of the core clock genes and the lipid metabolism genes were induced by the high-fat diet (HFD) in the liver tissues of T. sinensis. This result provides experimental and theoretical data for the mass breeding and production of T. sinensis in our country.

Growth is an important trait in aquaculture that is influenced by various factors, among which genetic regulation plays a crucial role. Megalobrama amblycephala, one of the most important freshwater species in China, exhibits wide variations in body mass among individuals of the same age within the same pool. But the molecular mechanisms underlying wide variation in body mass remain unclear. Here, we performed muscle histological and transcriptome analysis of muscle tissues from Fast-Growing (FG) and Slow-Growing (SG) M. amblycephala at the age of 4 months old (4 mo) and 10 months old (10 mo) to elucidate its muscle development and growth mechanism. The muscle histological analysis showed smaller diameter and higher total number of muscle fibers in FG compared to SG at 4 mo, while larger diameter and total number of muscle fibers were detected in FG at 10 mo. The transcriptome analysis of muscle tissue detected 1171 differentially expressed genes (DEGs) between FG and SG at 4 mo, and 718 DEGs between FG and SG at 10 mo. Furthermore, 44 DEGs were consistently up-regulated in FG at both 4 mo and 10 mo. Up-regulated DEGs in FG at 4 mo were mainly enriched in the pathways related to cell proliferation, while down-regulated DEGs were significantly enriched in cell fusion and muscle contraction. Up-regulated DEGs in FG at 10 mo were mainly enriched in the pathways related to cell proliferation and protein synthesis. Therefore, these results provide novel insights into the molecular mechanism of M. amblycephala muscle growth at different stages, and will be of great guiding significance to promote the fast growth of M. amblycephala.

The expression changes of high-mobility group box 1 (HMGB1) in the mouse cochlea have recently been implicated in noise-induced hearing loss, suggesting that HMGB1 participates in regulating cochlear function. However, the precise role of HMGB1 in the auditory system remains largely unclear. This study aimed to investigate its function in the developing mouse cochlea by examining the expression pattern of HMGB1 in the mouse cochlea from embryonic day (E) 18.5 to postnatal day (P) 28 using double immunofluorescence on frozen sections. Our findings revealed that HMGB1 was extensively expressed in the cell nucleus across various regions of the mouse cochlea, including the organ of Corti. Furthermore, its expression underwent developmental regulation during mouse cochlear development. Specifically, HMGB1 was found to be localized in the tympanic border cells at each developmental stage, coinciding with the gradual anatomical in this region during development. In addition, HMGB1 was expressed in the greater epithelial ridge (GER) and supporting cells of the organ of Corti, as validated by the supporting cell marker Sox2 at P1 and P8. However, at P14, the expression of HMGB1 disappeared from the GER, coinciding with the degeneration of the GER into the inner sulcus cells. Moreover, we observed that HMGB1 co-localized with Ki-67-positive proliferating cells in several cochlear regions during late embryonic and early postnatal stages, including the GER, the tympanic border cells, cochlear lateral wall, and cochlear nerves. Furthermore, by dual-staining Ki-67 with neuronal marker TUJ1 and glial marker Sox10, we determined the expression of Ki-67 in the neonatal glial cells. Our spatial-temporal analysis demonstrated that HMGB1 exhibited distinct expression patterns during mouse cochlear development. The co-localization of HMGB1 with Ki-67-positive proliferating cells suggested that HMGB1 may play a role in cochlear development.

The application of packing agents affects the final surgical outcomes in treating otitis media (OM) and introduces the risk of infection. To decrease the infectious risks of packing agents and even introduce positive bacteriostatic functions, a kind of PPDO-grafted Ag-incorporated TiO2 nanoparticles (Ag@TiO2-PPDO NP)-coated gauzes were prepared by a solution immersion method. Morphologies and in vitro Ag+ releasing of Ag@TiO2-PPDO NP coated gauzes were determined by scanning electron microscope (SEM) and inductively coupled plasma-mass spectrum (ICP-Ms). Ag@TiO2-PPDO NP could respond to visible light, which might make Ag@TiO2-PPDO NP inhibit the proliferation of bacteria continually and positively with irradiation of visible light. Then the bacteriostatic effects of these gauzes on OM pathogens were investigated in vitro and in vivo. These gauzes could inhibit the proliferation of pathogenic Staphylococcus aureus (S. aureus) and Streptococcus pneumoniae (S. pneumoniae) in vitro and rat subcutaneous infection models. Specifically, the bacteriostatic effect of these gauzes on S. aureus and S. pneumoniae could be enhanced with irradiation by visible light in vitro. Further, the rat external auditory canal infection model verified the enhanced bacteriostatic effect of Ag@TiO2-PPDO-coated gauzes on S. aureus with irradiation by visible light. The Ag@TiO2-PPDO-coated gauzes are promising for packing materials after OM surgery and could reduce postoperative antibiotic requirements.

Curcumae Longae Rhizoma (turmeric), Curcumae Radix and Curcumae Rhizoma are derived from the Curcuma species, and have gradually become three of the most commonly used medicinal herbs in China due to their different origins, processing methods and medicinal part. These three herbs have certain similarities in morphology, chemical composition, and pharmacological effects. All three of these herbs contain curcuminoids and volatile oil compounds, which exhibit anti-inflammatory, anti-tumor, antioxidant, and neuroprotective properties, although modern clinical applications have their own requirements. At present, there is no systematic guidelines for the clinical application of these three of Curcuma species; consequently, there is a high risk of unwanted phenomena associated with the mixing and indiscriminate use of these herbs. In this review, we focus predominantly on morphology, chemical composition, and the pharmacological activity of these three Curcuma herbs and summarize the current status of research in this field. Our goal is to provide a better understanding of clinical value of these Curcuma species so that we can provide reference guidelines for their further development, utilization and rational clinical application.

Abstract Flexible endoscopic evaluation of swallowing (FEES) is considered the gold standard in diagnosing oropharyngeal dysphagia. Recent advances in deep learning have led to a resurgence of artificial intelligence-assisted computer-aided diagnosis (AI-assisted CAD) for a variety of applications. AI-assisted CAD would be a remarkable benefit in providing medical services to populations with inadequate access to dysphagia experts, especially in aging societies. This paper presents an AI-assisted CAD named FEES-CAD for aspiration and penetration detection on video recording during FEES. FEES-CAD segments the input FEES video and classifies penetration, aspiration, residue in the vallecula, and residue in the hypopharynx based on the segmented FEES video. We collected and annotated FEES videos from 199 patients to train the network and tested the performance of FEES-CAD using FEES videos from other 40 patients. These patients consecutively underwent FEES between December 2016 and August 2019 at Fukushima Medical University Hospital. FEES videos were deidentified, randomized, and rated by FEES-CAD and laryngologists with over 15 years of experience in performing FEES. FEES-CAD achieved an average Dice similarity coefficient of 98.6 $$\%$$ % . FEES-CAD achieved expert-level accuracy performance on penetration (92.5 $$\%$$ % ), aspiration (92.5 $$\%$$ % ), residue in the vallecula (100 $$\%$$ % ), and residue in the hypopharynx (87.5 $$\%$$ % ) classification tasks. To the best of our knowledge, FEES-CAD is the first CNN-based system that achieves expert-level performance in detecting aspiration and penetration.

Abstract Background Tripartite motif (TRIM) family genes get involved in the pathogenesis and development of various biological processes; however, the prognostic value of TRIM genes for idiopathic pulmonary fibrosis (IPF) needs to be explored. Methods We acquired gene expression based on bronchoalveolar lavage (BAL) cells and clinical data of three independent IPF cohorts in the GSE70866 dataset from the Gene expression omnibus (GEO) database. Differentially expressed TRIM genes (DETGs) between IPF patients and healthy donors were identified and used to establish a risk signature by univariate and multivariate Cox regression analysis in the training cohort. The risk signature was further validated in other IPF cohorts, and compared with previously published signatures. Moreover, we performed functional enrichment analysis to explore the potential mechanisms. Eventually, the quantitative real time PCR was conducted to validate the expressions of the key genes in BAL from 12 IPF patients and 12 non-IPF controls from our institution. Results We identified 4 DETGs including TRIM7, MEFV, TRIM45 and TRIM47 significantly associated with overall survival (OS) of IPF patients (P

Celastrol is a promising antitumor drug candidate, but the poor water solubility and cytotoxicity limit its clinical application. Herein, we synthesized a Celastrol (Cel)-chitosan oligosaccharide (CSO) conjugate (Cel-CSO) for drug delivery. Celastrol was conjugated to a CSO backbone via amide bond formation, which was verified by infrared spectrum (IR) analyses. The Cel-CSO contained ∼10 wt% of Celastrol showed excellent aqueous solubility (18.6 mg/mL) in comparation with the parent Celastrol. Cel-CSO significantly inhibited tumor growth, induced apoptosis, and effectively suppressed tumor metastasis in human pancreatic cancer cells (BxPC-3). While the cytotoxicity of Cel-CSO in hepatic cells (HL7702) was lower than that of the free Celastrol. Cel-CSO enhanced the anticancer efficacy, promoted the circulation time of Celastrol, and reduced the subacute toxicity, which indicated that CSO can be a promising Celastrol delivery system for pancreatic cancer therapy.

Objective The objective of this study was to investigate the in vitro fermentation profiles of different soybean oligosaccharides (SBOs) and their effects on skatole production and cecal microbiota of broilers. Methods Five SBOs with varying main component contents were fermented using an in vitro batch incubation inoculated with broiler cecal microbiota. Gas production was recorded automatically, skatole, indole and short-chain fatty acids (SCFAs) were determined using high-performance liquid chromatography, and microbial changes were analyzed using 16S DNA gene sequencing. Results The addition of SBOs increased (p

ABSTRACT: The aim of this study was to explore the effects of dietary fermented feed addition on growth performance, immune organ indices, serum biochemical parameters, cecal odorous compound production, and the bacterial community in broilers. A total of 480 broiler chicks (1-day-old) were randomly assigned to 6 groups, including a basal diet (control group), a basal diet supplemented with 10, 15, 20, and 25% dried fermented feed, and 10% wet fermented feed. Each group contained 8 replicates of 10 chicks each. The results showed that fermentation increased (P < 0.05) the total acid level and the number of Lactobacillus, Yeast, and Bacillus. The 15% dried fermented feed group had an increased (P < 0.05) body weight (BW) than the control, while the 25% dried fermented feed group had the lowest (P < 0.05) BW on 42 d. Compared to the control group, the feed intake (FI) was increased (P < 0.05) in the 10, 15% dried and 10% wet fermented feed groups from 22 to 42 d and from 1 to 42 d. No significant difference (P > 0.05) was observed in feed conversion ratio (FCR) among all groups. Supplementation with fermented feed increased (P < 0.05) the bursa of Fabricius index but not (P > 0.05) the thymus and spleen indices. Compared with the control, the broilers fed fermented feed had increased (P < 0.05) serum total protein, albumin, globulin, IgA, IgG, IgM, lysozyme, complement 3, and complement 4 levels. The cecal concentrations of acetic acid, propionic acid, butyric acid, and lactic acid were increased and the pH values were decreased in the fermented feed groups (P < 0.05). Among the groups, the 15% dried fermented feed group showed the lowest concentrations of skatole and indole in the cecum (P < 0.05). The composition of the cecal microbiota was characterized, in which an increased abundance of Ruminococcaceae, Lactobacillaceae, and unclassified Clostridiales and a decreased abundance of Rikenellaceae, Lachnospiraceae, and Bacteroidaceae were found in the fermented feed groups. Taken together, dietary fermented feed supplementation can improve growth performance, immune organ development, and capacity and decrease cecal odorous compound production, which may be related to the regulation of microbial composition.

DNA methylation and demethylation are crucial epigenetic modification and regulation for animal development, and their dynamic changes may affect skeletal muscle development. The ten-eleven translocation (Tet) family proteins are demethylases which are involved in the dynamic changes of DNA methylation. However, the expression pattern of Tet family genes and their role in myogenesis in fish remains unclear. In this study, the temporal and spatial expression profiles of Tet1, Tet2 and Tet3 were assayed with RT-qPCR techniques in Chinese perch, Siniperca chuatsi. The obtained data showed that three Tet family genes were differentially expressed at different development stages. Tet1 was expressed low at blastula stage, but highly expressed at gastrula stage, then remained low until hatching. The expressions of Tet2 and Tet3 were significantly increased at late gastrula and kept high expression before hatching stage. At the spatial level, the Tet1 expression was highest in gill tissue, moderate level in brain and slow muscle. Tet2 was similar to that of Tet1 except that it was expressed at a lower level in slow muscle, and Tet3 exhibited a higher expression level in gill and brain, a moderate level in fast muscle. Cosinor analysis turned out that the expression of Tet1 and Tet2 displayed a significant daily rhythm in fast muscle, but Tet3 did not show daily rhythmicity. Inhibiting the activity of Tet1/2 proteins by injecting Bobcat339 significantly reduced the expression of MyoD and MRF4, but not MyoG and Myf5, by which leads to the increase of the number of satellite cells and proliferating myoblasts. Together, the results suggest that Tet1/2 may target to MyoD and MRF4 resulted in DNA demethylation and promoting their expression, thus stimulating myoblast differentiation.

Hydrogen evolution reaction (HER) is a vital step in water electrolysis toward H2 production. However, conventional nanocatalysts lack uniform size, composition, structure, and a homogeneous chemical coordination environment, causing the retrieval of an unambiguous structure–performance relationship to be extremely challenging. Owing to its ultra-small size, definitive composition, well-defined structure, and uniform chemical environment at the atomic level, atomically precise Au nanoclusters can serve as a model catalyst to improve understanding of the relationship between the structure and its catalytic properties. First, this review describes the fundamental mechanism and significance of HER and highlights the unique advantages of employing Au nanoclusters as a model catalyst. Then, the recent progress involving the promotion and catalysis of HER by Au and Au-alloy nanoclusters is discussed, with a focus on elaborating the structure–performance relationship. The key factors affecting the catalytic performance, including but not limited to the electronic interaction, interfacial effect, size effect, charge state, ligand effect, metal core composition, single-atom doping, and geometric configuration effect, are analyzed with explicit examples. Finally, the current critical challenges involved in this process and future perspectives are discussed. We hope that this review can shed light on the design of efficient and stable coinage metal-nanocluster-based catalysts toward electrochemical H2 production and beyond.

Abstract Deep simulations have gained widespread attention owing to their excellent acceleration performances. However, these methods cannot provide effective collision detection and response strategies. We propose a deep interactive physical simulation framework that can effectively address tool-object collisions. The framework can predict the dynamic information by considering the collision state. In particular, the graph neural network is chosen as the base model, and a collision-aware recursive regression module is introduced to update the network parameters recursively using interpenetration distances calculated from the vertex-face and edge-edge tests. Additionally, a novel self-supervised collision term is introduced to provide a more compact collision response. This study extensively evaluates the proposed method and shows that it effectively reduces interpenetration artifacts while ensuring high simulation efficiency.