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Although microsurgical vasoepididymostomy (MVE) is an effective treatment for epididymal obstructive azoospermia, some patients may experience delayed patency or suboptimal semen parameters after patency. However, research into patency time, semen quality postpatency, and associated influencing factors remains limited. This study aimed to address these issues by evaluating 181 patients who underwent at least one-sided MVE employing asingle-armed longitudinal intussusception vasoepididymostomy technique, with a follow-up period of over 12 months for 150 patients. The overall patency rate was 75.3%, with 86.0% of patients achieving patency within 6 months following MVE. Unexpectedly, factors such as age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, and the site of anastomosis showed no correlation with patency time. Nonetheless, our univariate and multivariate linear regression analysis indicated that only the site of anastomosis was positively correlated with and could independently predict postoperative total motile sperm count. Therefore, the site of anastomosis might serve as a predictor for optimal postoperative semen quality following the MVE procedure.

Abstract Magnetic kagome materials provide a fascinating playground for exploring the interplay of magnetism, correlation and topology. Many magnetic kagome systems have been reported including the binary Fe m X n (X = Sn, Ge; m:n = 3:1, 3:2, 1:1) family and the rare earth RMn6Sn6 (R = rare earth) family, where their kagome flat bands are calculated to be near the Fermi level in the paramagnetic phase. While partially filling a kagome flat band is predicted to give rise to a Stoner-type ferromagnetism, experimental visualization of the magnetic splitting across the ordering temperature has not been reported for any of these systems due to the high ordering temperatures, hence leaving the nature of magnetism in kagome magnets an open question. Here, we probe the electronic structure with angle-resolved photoemission spectroscopy in a kagome magnet thin film FeSn synthesized using molecular beam epitaxy. We identify the exchange-split kagome flat bands, whose splitting persists above the magnetic ordering temperature, indicative of a local moment picture. Such local moments in the presence of the topological flat band are consistent with the compact molecular orbitals predicted in theory. We further observe a large spin-orbital selective band renormalization in the Fe $${{{{\rm{d}}}}}_{{xy}}+{{{{\rm{d}}}}}_{{x}^{2}-{y}^{2}}$$ d x y + d x 2 − y 2 spin majority channel reminiscent of the orbital selective correlation effects in the iron-based superconductors. Our discovery of the coexistence of local moments with topological flat bands in a kagome system echoes similar findings in magic-angle twisted bilayer graphene, and provides a basis for theoretical effort towards modeling correlation effects in magnetic flat band systems.

To inhibit the development of adaptive acid tolerance response (ATR) and concurrent multiple stress resistance in Salmonella induced by the residual acid environment from carcass decontamination by organic acid spraying, the inhibitory effect of the addition of oregano essential oil and calcium chloride at different subinhibitory concentrations during acid adaptation on the ATR of Salmonella was investigated by determining the survival ability of Salmonella in acidic, thermal, hyperosmotic and oxidative environments before and after adaptation, and the possible mechanism was explored by determining the relative expression of stress resistance genes before and after treatments. The results indicated that the residual acid (pH 5.4) generated during carcass processing might induce ATR and heat-resistant cross-protection in Salmonella, suggesting a potential food safety risk. After 2 h treatment with hydrochloric acid at pH 3, the loss of the adapted strain in the 1/2 MIC oregano essential oil and 10 mmol/L CaCl2 treatment group increased by 1.32 (lg(CFU/mL)) compared with the control group, and oregano essential oil combined with CaCl2 had a synergistic inhibitory effect on ATR. The addition of oregano essential oil and calcium chloride during acid adaptation down-regulated the expression of the phoP and rpoS genes, which in turn intervened in the two-component system and global transcription factors, thereby suppressing ATR development. Sub-inhibitory concentrations of oregano essential oil inhibited the formation of the acid and heat resistance of acid-adapted Salmonella, but increased the resistance to hyperosmosis, whereas CaCl2 at a concentration of 10 mmol/L combined with sub-inhibitory concentrations of oregano essential oil reduced the osmotic resistance. The results of the current study help to understand the effects of essential oil and CaCl2 on the acid adaptation process of Salmonella and provide a theoretical basis for risk control for the use of organic acids in the beef industry.

Abstract Background Although the Stress-Coping Model (SCM) has been widely used to explain the coping process of individuals facing stressful situations, its applicability to caregivers of elderly people with dementia (PwD) in China needs to be further investigated. Furthermore, the role of external resources in caregivers stress coping is not yet clear. Therefore, our study aimed to investigated the mediating and moderating mechanisms between family burden and psychological distress in PwD caregivers based on the SCM. Methods A cross-sectional study, with 193 pairs of PwD and caregivers completed the self-designed questionnaire, Family Burden Scale of Disease, Kessler Psychological Distress Scale, General Self-Efficacy Scale, Simplified Coping Style Question, The Family Adaptation and Cohesion Evaluation Scales II-CV and Social Support Rating Scale. Partial least squares-structural equation modeling (PLS-SEM) analyzed the mediating and moderating effects. Results Family burden positively correlated with psychological distress; the chain mediation effects of self-efficacy and positive coping between family burden and psychological distress was significant; the interaction term (family function_positive coping) did not but (social support_positive coping) had a significant positive impact on psychological distress. Conclusions The findings provides a practical basis for the use of SCM in informal caregivers of elderly PwD, assists understanding the mechanism of the relationship between family burden and psychological distress. And it supplies new perspectives for reducing the negative psychological health status and a theoretical basis for designing interventions for caregivers.

Abstract In the digital age, the application of Artificial Intelligence (AI) has become an irreversible trend, with its potential in the field of education being particularly noteworthy. However, there are currently few AI education programs for children in Taiwan, and there is a lack of systematic teaching resources and methods, which poses a major challenge to the promotion of AI education. To address this challenge, this study designed a tailor-made AI curriculum for children in Taiwan, aimed at enhancing their foundational knowledge in the AI field and skills in using generative AI. This study was conducted in Taiwan, involving 30 elementary school students from grades 3 and 4, employing a single-group pre-test and post-test research design. Data were collected and analyzed through pre-and post-tests on AI knowledge quizzes and AI knowledge self-assessment, as well as the expert consensual assessment technique and the pupils’ attitude toward technology survey questionnaire. Research shows that students who participated in the AI course significantly improved their test scores on AI knowledge before and after the course. The students AI knowledge increased by 62.75%, demonstrating the course’s effectiveness and showing a positive attitude towards AI technology. Additionally, the student’s project outcomes demonstrated a high level of creativity. The students exhibited an enhanced interest and positive attitude towards learning AI, expressing a willingness to participate in more AI educational courses. This work provides valuable experience and guidance for the future integration of AI technology in children’s education, offering practical guidelines for teachers and researchers on how to effectively teach AI knowledge, as well as serving as a robust reference for educational policy makers in formulating strategies to promote AI education.

Abstract Periodically driven quantum systems exhibit a diverse set of phenomena but are more challenging to simulate than their equilibrium counterparts. Here, we introduce the Quantum High-Frequency Floquet Simulation (QHiFFS) algorithm as a method to simulate fast-driven quantum systems on quantum hardware. Central to QHiFFS is the concept of a kick operator which transforms the system into a basis where the dynamics is governed by a time-independent effective Hamiltonian. This allows prior methods for time-independent simulation to be lifted to simulate Floquet systems. We use the periodically driven biaxial next-nearest neighbor Ising (BNNNI) model, a natural test bed for quantum frustrated magnetism and criticality, as a case study to illustrate our algorithm. We implemented a 20-qubit simulation of the driven two-dimensional BNNNI model on Quantinuum’s trapped ion quantum computer. Our error analysis shows that QHiFFS exhibits not only a cubic advantage in driving frequency ω but also a linear advantage in simulation time t compared to Trotterization.

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.

Pesticide residues treatment is a crucial issue for both agricultural production and environmental protection. In recent years, designing self-cleaning nanoformulations has emerged as a promising strategy for reducing pesticide residues in a convenient and cost-effective manner. However, traditional physical blending methods of photodegradation reagents with nanocarriers have limitations in terms of pesticide residue degradation efficiency and active ingredient efficacy. Here, a new type of timing self-cleaning nanoherbicide dicamba@mSiO2/ATA/TiO2 with a triple structure was fabricated. Dicamba, a widely used herbicide that was attracting increasing concern over its high efficiency and broad spectrum, was selected as the model herbicide and loaded on the mSiO2 shell. In the stage of pesticide release, the TiO2 and dicamba were separated by the timing-barrier. Therefore, the efficacy of dicamba was not affected by the photocatalyst. During the release process, the ATA layer continuously absorbed the reactive oxygen species (ROS) produced by TiO2 and was gradually degraded. Finally, the barrier was destroyed, and the residual dicamba in the carrier was degraded by TiO2. Compared with the traditional physical blending method, this triple structure avoided the degradation of active ingredients by photocatalysts during the pesticide release period. The experimental results suggested that this nanoformulation improved the efficacy of the herbicide, and reduced the pesticide residues, providing a new approach for self-cleaning nanopesticides research.

Abstract Background Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. Method This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22–27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. Result A total of 2004 preterm infants with gestational ages of 22–27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22–22+ 6w, 23–23+ 6w, 24–24+ 6w, 25–25+ 6w, 26–26+ 6w, and 27–27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. Conclusion The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25–27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries.

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 The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

BackgroundAt present, the available evidence regarding the relationship between duration of phenoxybenzamine use and postoperative delirium is inadequate in suspected adrenal pheochromocytoma.ObjectiveTo understand how changes in the duration of phenoxybenzamine use may affect postoperative delirium. The secondary objective of this study is to explore how the duration of phenoxybenzamine use may jointly influence postoperative delirium together with other interacting variables.MethodsWe conducted a retrospective cohort study involving 527 participants with a preoperative diagnosis of suspected pheochromocytoma. CT characteristics, preoperative preparation, intraoperative infusion, estimated bleeding, use of intraoperative vasoactive drugs, and outcomes were obtained from all participants. Logistic regression and interaction effects were utilized to substantiate the research objectives.ResultsA total of 108 (20.5%) developed postoperative delirium, which was seen in 37 (18.0%) in the pheochromocytoma group and 71 (22.0%) in the non-pheochromocytoma group. The incidence of postoperative delirium showed no statistically significant differences in the two groups. A positive association between the duration of phenoxybenzamine use and the risk of postoperative delirium was observed (OR = 1.05, 95%CI = 1.03–1.08, p

Bioactive peptides have rich nutritional value and multiple biological functions, which plays a crucial role in health of aquatic animals. In this study, we screened crayfish shell bioactive peptides based on molecular simulation, and analyzed their effects on oxidative stress and lipid metabolism disorders induced by excessive copper (Cu) diet in zebrafish. The protein hydrolysates were prepared by enzymatic hydrolysis of crayfish shell protein using trypsin, and the peptide sequences were determined by LC-MS/MS. The peptide LPLWPY (LY-6, the molecular weight is 787.94 Da) identified using peptide database PeptideRanker prediction and molecular docking showed strong antioxidant potential. In vivo experiments of zebrafish showed that dietary supplementation of LY-6 peptide significantly improved the adverse effects of oxidative stress and abnormal lipid metabolism caused by excessive Cu diet. The results of zebrafish primary hepatocytes revealed that LY-6 peptide promoted the antioxidant capacity and lipid metabolism normalization of cells by regulating nrf2 and pparγ signaling pathways, thereby reducing oxidative stress and lipid accumulation. The findings of this study revealed that antioxidant peptide LPLWPY with strong from crayfish shell protein hydrolysates could alleviate oxidative stress and lipid metabolism abnormalities caused by excessive Cu diet in zebrafish, thus could be recommended as a potential functional feed ingredient for fish nutrition. It provides theoretical basis and reference for aquatic animal nutrition regulation and development of novel feed additives.

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.

Introduction: This case report documents an exceptionally rare hepatic glomus tumor, contributing valuable insights to the diagnosis and differential diagnosis of such tumors. Main symptoms and important clinical findings: A 58-year-old male was admitted in 2023 due to unexplained elevation of bilirubin discovered during routine laboratory tests. The patient denied any symptoms, and physical examination revealed no positive findings. Laboratory tests indicated elevated bilirubin, while serum tumor markers remained within normal ranges. Contrast-enhanced computed tomography revealed an indistinctly bordered hepatic mass, displaying uneven and marked enhancement in the arterial phase and sustained enhancement in the venous phase. The main diagnoses, therapeutic interventions, and outcomes: The patient underwent laparoscopic partial hepatectomy, and pathological examination suggested a spindle cell tumor of mesenchymal origin. Immunohistochemistry confirmed positive staining for smooth muscle actin, leading to the final diagnosis of a hepatic glomus tumor with undetermined malignant potential. Follow-up at 6 months postoperatively showed no signs of metastasis or recurrence. Conclusion: This case underscores the subtle radiological distinctions of hepatic glomus tumors, resembling hemangiomas but manifesting unique features. Additionally, the crucial role of immunohistochemistry in achieving a definitive diagnosis is emphasized in this report.

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.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10–100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

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.

In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.

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.

Abstract Background Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. Methods This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. Results The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p

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

Abstract Non-volatile phase-change memory devices utilize local heating to toggle between crystalline and amorphous states with distinct electrical properties. Expanding on this kind of switching to two topologically distinct phases requires controlled non-volatile switching between two crystalline phases with distinct symmetries. Here, we report the observation of reversible and non-volatile switching between two stable and closely related crystal structures, with remarkably distinct electronic structures, in the near-room-temperature van der Waals ferromagnet Fe5−δ GeTe2. We show that the switching is enabled by the ordering and disordering of Fe site vacancies that results in distinct crystalline symmetries of the two phases, which can be controlled by a thermal annealing and quenching method. The two phases are distinguished by the presence of topological nodal lines due to the preserved global inversion symmetry in the site-disordered phase, flat bands resulting from quantum destructive interference on a bipartite lattice, and broken inversion symmetry in the site-ordered phase.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl− transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl− transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl− concentration ([Cl−]i) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl−]i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

Abstract Background Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. Method Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. Results Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P

C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.

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).

For the problem of control of flexible linear double inverted pendulum (FLDIP), considering that the method of obtaining LQR parameters through traditional manual trial-and-error is too cumbersome, and the basic particle swarm optimization algorithm has a slower convergence speed and is prone to a local optimal solution, in this paper, a control method is proposed that it can achieve autonomous optimization based on improved the particle swarm optimization (PSO) algorithm. Firstly, the mathematical model of the FLDIPs is given to analyse the stability of the system. Then, the PSO algorithm is improved from the perspective of dynamically adjusting inertia weights to optimize linear quadratic regulator (LQR) parameters. Finally, through simulation comparison with the LQR control effect obtained by the manual trial and error method, the feasibility of the improved PSO algorithm is verified. This method can not only improve the control performance of the system but also effectively overcome the problem of blindness in selecting Q for traditional LQR optimal control.

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.

BackgroundCircadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity.MethodsA total of 221 preterm infants of gestational age 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (PFDR = 0.045) and the over-dominant model (PFDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12–0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64–10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P

Abstract Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non‐small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1‐AS1) in the progression of NSCLC were explored. The increased level of N6‐methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1‐AS1. Subsequently, high‐expressed PHKA1‐AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1‐AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1‐AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1‐AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

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.

This study investigated the effect of resveratrol on muscle fiber type transformation in bovine myotubes. Cell viability and related metabolic enzyme activities were measured by methyl thiazolyl tetrazolium (MTT) and colorimetric assays, and myogenic regulatory factors (MRFs), myosin heavy chains (MyHCs), and gene and protein expression related to mitochondrial biogenesis were determined. The results showed that resveratrol treatment significantly increased the gene expression of Myf5, Myf6, MyoG, and MyoD (P < 0.05) and promoted the differentiation of bovine myotubes. Resveratrol significantly increased slow MyHC expression and decreased fast MyHC expression, while upregulating the mRNA expression levels of MyHC I and MyHC IIa and downregulating the mRNA expression levels of MyHC IIx and MyHC IIb (P < 0.05). Resveratrol also significantly increased succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) activity and decreased lactic dehydrogenase (LDH) activity (P < 0.05). In addition, resveratrol increased the gene and protein expression levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), nucleus respiratory factors-1 (NRF-1), mitochondrial transcription factor A (TFAM) (P < 0.05). Addition of the SIRT1 inhibitor 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (EX527) significantly attenuated resveratrol-induced muscle fiber type transformation (P < 0.05), and the promoting effect of resveratrol on the gene and protein expression of SIRT1, PGC-1α, NRF-1, and TFAM (P < 0.05). Taken together, resveratrol can promote mitochondrial biogenesis and consequently muscle fiber type transformation by activating the SIRT1/PGC-1α signaling pathway.

Abstract Background Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. Methods qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. Results The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. Conclusions The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

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 Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

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.

In order to explore the impact of circadian disturbance on erectile function, we randomly divided 24 adult male rats into groups of control (light on at 8:00 a.m. and off at 8:00 p.m.), dark/dark (DD; constant dark), light/light (LL; constant light), and shift dark/light (DL; light off at 8:00 a.m. and on at 8:00 p.m.). Four weeks later, erectile function was measured and corpora cavernosa were harvested for analysis. The maximum intracavernous pressure (mICP) and mICP/mean arterial pressure (MAP) ratio in the DD, LL, and DL groups were significantly lower than that in the control group. The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase (eNOS), while DD, LL, and DL showed reduced neuronal nitric oxide synthase (nNOS) at both mRNA and protein levels. The production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was inhibited by altered light/dark cycles to varying degrees. Circadian disturbance impaired endothelial function and contributed to erectile dysfunction. For the core circadian elements, mRNA expression of circadian locomotor output cycles kaput (Clock) and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) was elevated in the DL group, but their protein expression was not significantly changed. DD, LL, and DL increased period 1 (Per1) and Per3 levels, while LL and DL increased PER1 levels. No significant difference was found for Per2 levels, and PER2 and PER3 concentrations were not significantly changed. Moreover, LL and DL significantly increased cryptochrome-1 (CRY1) and CRY2 at both mRNA and protein levels. The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function. Meanwhile, the core circadian elements were detected in the corpora cavernosa, but these were disrupted. However, which circadian element regulates erectile function and how it works need further analysis.