Modifiable risk factors of immediate and long-term outcomes in the operable and inoperable with left-sided infective endocarditis.

Objectives: To evaluate the outcomes of left-sided infective endocarditis that can be operated on and cannot be operated on, and to focus on modifiable risk factors for immediate and long-term mortality. Methods: This study retrospectively investigated patients with left-sided infective endocarditis who occurred in our medical center between January 2006 and November 2022. Results: 48 in-hospital deaths occurred (5.8 %, 48/832). We identified time from symptoms to admission and symptomatic neurological complications to be risk factors for multiple organ failure upon admission. Time from symptoms to admission and vegetation size in group of isolated medical treatment were significantly shorter than those in the group of heart operation. We also found that preoperative neurological complications, annulus destruction, levels of serum creatinine at 24 and 48 h post heart operation, and perivalvular leakage are risk factors for in-hospital mortality post heart operation. With 148 µmol/L as a cutoff level, the diagnostic sensitivity and specificity of serum creatinine level 48 h post surgery for in-hospital mortality post cardiac surgery are 100 % and 81.6 %, respectively. We found that vegetation size, ICU stay, postoperative serum creatinine at 48 h, left ventricular end diastolic size postoperative, and red blood cell transfusion were associated with all-time mortality. Conclusions: Early diagnosis and treatment, improvement of surgical techniques, good protection for heart, kidney and blood and close follow-up are advocated to conduce to better immediate and long-term outcomes of the operable and inoperable with left-sided infective endocarditis.

A Bispecific Chimeric Aptamer Design Platform Based on c-MET Aptamer with a Replaceable Redundant Region.

Molecular engineering enables the creation of aptamers with novel functions, but the prerequisite is a deep understanding of their structure and recognition mechanism. The cellular-mesenchymal epithelial transition factor (c-MET) is garnering significant attention due to the critical role of the c-MET/HGF signaling pathway in tumor development and invasion. This study reports a strategy for constructing novel chimeric aptamers that bind to both c-MET and other specific proteins. c-MET was identified to be the molecular target of a DNA aptamer, HF3-58, selected through cell-SELEX. The binding structure and mechanism of HF3-58 with c-MET were systematically studied, revealing the scaffold, recognition, and redundancy regions. Through molecular engineering design, the redundancy region was replaced with other aptamers possessing stem-loop structures, yielding novel chimeric aptamers with bispecificity for binding to c-MET and specific proteins. A chimeric bispecific aptamer HF-3b showed the ability to mediate the adhesion of T-cells to tumor cells, suggesting the prospective utility in tumor immunotherapy. These findings suggest that aptamer HF3-58 can serve as a molecular engineering platform for the development of diverse multifunctional ligands targeting c-MET. Moreover, comprehensive understanding of the binding mechanisms of aptamers will provide guidance for the design of functional aptamers, significantly expanding their potential applications.

Chlorogenic acid can improve spermatogenic dysfunction in rats with varicocele by regulating mitochondrial homeostasis and inhibiting the activation of NLRP3 inflammasomes by oxidative mitochondrial DNA and cGAS/STING pathway.

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

Long-term residue returning increased subsoil carbon quality in a rice-wheat cropping system.

Residue returning (RR) was widely implemented to increase soil organic carbon (SOC) in farmland. Extensive studies concentrated on the effects of RR on SOC quantity instead of SOC fractions at aggregate scales. This study investigated the effects of 20-year RR on the distribution of labile (e.g., dissolved, microbial biomass, and permanganate oxidizable organic) and stable (e.g., microbial necromass) carbon fractions at aggregate scales, as well as their contribution to SOC accumulation and mineralization. The findings indicated a synchronized variation in the carbon content of bacterial and fungal necromass. Residue retention (RR) notably elevated the concentration of bacterial and fungal necromass carbon, while it did not amplify the microbial necromass carbon (MNC) contribution to SOC when compared to residue removal (R0) in the topsoil (0-5 cm). In the subsoil (5-15 cm), RR increased the MNC contribution to SOC concentration by 21.2%-33.4% and mitigated SOC mineralization by 12.6% in micro-aggregates (P < 0.05). Besides, RR increased soil ß-glucosidase and peroxidase activities but decreased soil phenol oxidase activity in micro-aggregates (P < 0.05). These indicated that RR might accelerate cellulose degradation and conversion to stable microbial necromass C, and thus RR improved SOC stability because SOC occluded in micro-aggregates were more stable. Interestingly, SOC concentration was mainly regulated by MNC, while SOC mineralization was by dissolved organic carbon under RR, both of which were affected by soil carbon, nitrogen, and phosphorus associated nutrients and enzyme activities. The findings of this study emphasize that the paths of RR-induced SOC accumulation and mineralization were different, and depended on stable and labile C, respectively. Overall, long-term RR increased topsoil carbon quantity and subsoil carbon quality.

The development of Tibetan children's racial bias in empathy: The mediating role of ethnic identity and wrongfulness of ethnic intergroup bias.

OBJECTIVES: Individuals often automatically have more empathy for same-race members. However, there are no studies on racial bias in empathy (RBE) among Tibetan school-aged children. The present study aimed to examine the development of RBEs, including racial bias in cognitive empathy, affective empathy, and behavioral empathy, in Tibetan school-aged children. METHOD: In Experiment 1 (N = 108, aged 7-12), ethnic identity was primed using Tibetan and Han names. Then negative and neutral events were applied to measure the RBEs of Tibetan children. In Experiment 2 (N = 148, aged 7-12), negative events were replaced by pain events. In Experiment 3 (N = 60, aged 7-12), Tibetan children's ethnic identity and the awareness of the wrongfulness of ethnic intergroup bias were added to examine the underlying mechanism. RESULT: Results found that RBEs increased among Tibetan children aged 7-10 and decreased among those aged 11-12, Moreover, we analyzed age as a continuous variable and found that 10 years old was the inflection point in the development of RBEs in Tibetan children. Importantly, children aged 11-12 years old realized more wrongfulness of ethnic intergroup bias than children aged 7-10. The ethnic identity of Tibetan children aged 7-10 mediated the relation between age group and RBEs. And the wrongfulness of ethnic intergroup bias mediated the link between age group and RBEs in Tibetan children aged 9-12. CONCLUSION: Our study sheds light on the development of RBEs in Tibetan school-aged children and highlights the importance of identifying the appropriate timing for intervening in prejudice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Analgesic effect and safety of a half-dose transdermal buprenorphine patch after arthroscopic rotator cuff repair.

Objective: To retrospectively explore the effect of a half-dose buprenorphine transdermal patch for analgesia after arthroscopic rotator cuff repair (ARCR). Methods: This analysis was performed with clinical data from patients who received unilateral ARCR in our hospital between October 2017 and December 2020. The patients were divided into three groups (30 cases each). In group A (control group), 100 mg flurbiprofen axetil (FA) was administered twice a day for 5 days after surgery. In group B (experimental group), 100 mg FA was administered twice a day for 5 days and half (2.5 mg) of a buprenorphine transdermal patch was applied after surgery; an additional half (2.5 mg) patch was applied 3 days later. In group C (condition control group), 100 mg FA was administered twice a day for 5 days and a 5-mg patch was applied directly after surgery. The visual analog scale (VAS) was administered repeatedly 1 day before surgery and 1, 2, 3, 5, and 14 days after surgery in each group. The simple shoulder test (SST) score, range of shoulder forward elevation (FE), and external rotation (ER) were recorded preoperatively and 12 weeks postoperatively. Results: VAS scores on postoperative days 3 and 5 were significantly lower in groups B and C than in group A (p < 0.05). The VAS score on postoperative day 14 was significantly lower in group C than in group A (p < 0.05). The difference in VAS score between groups B and C was not significant (p > 0.05). All patients had significantly improved VAS scores, SST scores, FE, and ER at 12 weeks postoperatively. Conclusion: The half-dose buprenorphine transdermal patch had a good analgesic effect with minimal side effects after ARCR and did not delay the recovery of shoulder joint function.

Diagnostic prediction of gastrointestinal graft-versus-host disease based on a clinical- CT- signs nomogram model.

OBJECTIVE: Gastrointestinal graft-versus-host disease (GI-GVHD) is one of the complications that can easily occur after hematopoietic stem cell transplantation (HSCT). Timely diagnosis and treatment are pivotal factors that greatly influence the prognosis of patients. However, the current diagnostic method lacks adequate non-invasive diagnostic tools. METHODS: A total of 190 patients who suspected GI-GVHD were retrospectively included and divided into training set (n = 114) and testing set (n = 76) according to their discharge time. Least absolute shrinkage and selection operator (LASSO) regression was used to screen for clinically independent predictors. Based on the logistic regression results, both computed tomography (CT) signs and clinically independent predictors were integrated in order to build the nomogram, while the testing set was verified independently. The receiver operating characteristic (ROC), area under the curve (AUC), decision curve, and clinical impact curve were used to measure the accuracy of prediction, clinical net benefit, and consistency of diagnostic factors. RESULTS: Four key factors, including II-IV acute graft-versus-host disease (aGVHD), the circular target sign, multifocal intestinal inflammation, and an increased in total bilirubin, were identified. The combined model, which was constructed from CT signs and clinical factors, showed higher predictive performances. The AUC, sensitivity, and specificity of the training set were 0.867, 0.787, and 0.811, respectively. Decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) showed that the developed model exhibited a better prediction accuracy than the others. CONCLUSIONS: This combined model facilitates timely diagnosis and treatment and subsequently improves survival and overall outcomes in patients with GI-GVHD. CRITICAL RELEVANCE STATEMENT: GI-GVHD is one of the complications that can easily occur after HSCT. However, the current diagnostic approach lacks adequate non-invasive diagnostic methods. This non-invasive combined model facilitates timely treatment and subsequently improves patients with GI-GVHD survival and overall outcomes. KEY POINTS: • There is currently lacking of non-invasive diagnostic methods for GI-GVHD. • Four clinical CT signs are the independent predictors for GI-GVHD. • Association between the CT signs with clinical factors may improve the diagnostic performance of GI-GVHD.

Evaluation of clinical and imaging features for differentiating rhabdomyosarcoma from neuroblastoma in pediatric soft tissue.

Background: In this study, we developed a nomogram predictive model based on clinical, CT, and MRI parameters to differentiate soft tissue rhabdomyosarcoma (RMS) from neuroblastoma (NB) in children preoperatively. Materials and methods: A total of 103 children with RMS (n=37) and NB (n=66) were enrolled in the study from December 2012 to July 2023. The clinical and imaging data (assessed by two experienced radiologists) were analyzed using univariate analysis, and significant factors were further analyzed by multivariable logistic regression using the forward LR method to develop the clinical model, radiological model, and integrated nomogram model, respectively. The diagnostic performances, goodness of fit, and clinical utility of the integrated nomogram model were assessed using the area under the curve (AUC) of the receiver operator characteristics curve (ROC) with a 95% confidence interval (95% CI), calibration curve, and decision curve analysis (DCA) curves, respectively. Diagnostic efficacy between the model and radiologists' interpretations was examined. Results: The median age at diagnosis in the RMS group was significantly older than the NB group (36.0 months vs. 14.5 months; P=0.003); the fever rates in RMS patients were significantly lower than in patients with NB (0.0% vs.16.7%; P=0.022), and the incidence of palpable mass was higher in patients with RMS compared with the NB patients (89.2% vs. 34.8%; P<0.001). Compare NB on image features: RMS occurred more frequently in the head and neck and displayed homogeneous density on non-enhanced CT than NB (48.6% vs. 9.1%; 35.3% vs. 13.8%, respectively; all P<0.05), and the occurrence of characteristics such as calcification, encasing vessels, and intraspinal tumor extension was significantly less frequent in RMS children compared to children with NB (18.9% vs. 84.8%; 13.5% vs. 34.8%; 2.7% vs. 50.0%, respectively; all P <0.05). Two, three, and four features were identified as independent parameters by multivariate logistic regression analysis to develop the clinical, radiological, and integrated nomogram models, respectively. The AUC value (0.962), calibration curve, and DCA showed that the integrated nomogram model may provide better diagnostic performance, good agreement, and greater clinical net benefits than the clinical model, radiological model, and radiologists' subjective diagnosis. Conclusion: The clinical and imaging features-based nomogram has potential for helping radiologists distinguish between pediatric soft tissue RMS and NB patients preoperatively, and reduce unnecessary interventions.

Applying AVWEWM to ethical decision-making during autonomous vehicle crashes.

At present, a few scholars studied influencing factors, rules and mechanisms of decision-making in ethical dilemmas. Many factors have been identified, and a few rules and mechanisms have been proposed. However, due to the inability to evaluate the weight and role of each factor in decision-making, it is difficult to establish a computational decision-making model to solve ethical dilemmas. Therefore, entropy weighted method (EWM) and Attribute Value Weighted EWM (AVWEWM) are used to process 84 dilemmas respectively to evaluate the weight and role of each factor in decision-making, then decision-making models based on EWM and AVWEWM are constructed to make decisions during autonomous vehicle (AV) crashes respectively. Lastly, 40 dilemmas are designed to test both decision-making models. The test results indicate that both can make clear decision-making in 40 dilemmas. However, the decision-making by AVWEWM is more consistent with public opinion than EWM. In addition, according to the weight and role of each factor in decision-making, it can also provide a few references for traffic management and legal departments to formulate traffic laws and regulations for AV in the future.

How Society Anxiety Influences Attention Control in College Students: The Moderated Mediation Effect of Cognitive Flexibility and Resting-state Electroencephalography Activity.

Social anxiety is a prevalent issue among college students, adversely affecting their overall well-being. Drawing from the cognitive model of social anxiety and attention control theory, heightened levels of social anxiety may correspond to poorer attention control ability. However, little is known about the underlying cognitive mechanisms of the relationship between social anxiety and attention control. To address this research gap, the current study recruited a sample of 156 college students (56 women) who underwent self-report measures of social anxiety, cognitive flexibility, and attention control, followed by a resting-state EEG recording. The results revealed a significant negative predictive effect of social anxiety on attention control, with cognitive flexibility partially mediating this relationship. Furthermore, resting-state theta power emerged as a significant moderator, accentuating the negative impact of social anxiety on cognitive flexibility among individuals with lower theta power. In addition, frontal alpha asymmetry (FAA) demonstrated a moderating effect, with lower FAA intensifying the predictive influence of cognitive flexibility on attention control. Taken together, these results suggested that social anxiety can predict attention control either directly or indirectly via the mediating role of cognitive flexibility, and lower theta power and FAA has a risk amplification effect, which provide novel insights into the treatment and prevention of social anxiety and its negative impact on college students.

DNA four-way junction-driven dual-rolling circle amplification sandwich-type aptasensor for ultra-sensitive and specific detection of tumor-derived exosomes.

There is an urgent need to accurately quantify tumor-derived exosomes, which have emerged as promising non-invasive tumor diagnostic biomarkers. Herein, a bispecific-aptamer sandwich-type gold nanoparticle-modified electrochemical aptasensor was developed based on a four-way junction (4-WJ)-triggered dual rolling circle amplification (RCA)-assisted methylene blue (MB)/G-quadruplex strategy for extremely specific and sensitive exosome detection. This aptamer/exosome/aptamer sandwich-type design contained a CD63-specific aptamer and a cancerous mucin-1 (MUC1) protein-specific aptamer. The CD63 aptamer modified on a gold electrode captured exosomes, and then the sandwich-type aptasensor was formed with the addition of the MUC1 aptamer. The MUC1 aptamer's 3'-end sequence facilitated the formation of 4-WJ, assisted by a molecular beacon probe and a binary DNA probe. Subsequently, a dual-RCA reaction was triggered by binding to two cytosine-rich circle DNA templates at both ends of 4-WJ. Ultimately, dual-RCA products containing multiple G-quadruplex conformations were generated with the assistance of K+ to trap abundant MB indicators and amplify electrochemical signals. The aptasensor exhibited high specificity, sensitivity, repeatability, and stability toward MCF-7-derived exosomes, with a detection limit of 20 particles/mL and a linear range of 1 × 102 to 1 × 107 particles/mL. Moreover, it showed excellent applicability in clinical settings to recover exosomes in normal human serum. Our aptasensor is anticipated to serve as a versatile platform for detecting various specific aptamer-based targets in biomedical and bioanalytical applications.

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome-mediated Caspase-1/GSDMD pyroptosis pathway.

Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1ß, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.

Smart Tumor Cell-Derived DNA Nano-Tree Assembly for On-Demand Macrophages Reprogramming.

Without coordinated strategies to balance the population and activity of tumor cells and polarized macrophages, antitumor immunotherapy generally offers limited clinical benefits. Inspired by the "eat me" signal, a smart tumor cell-derived proximity anchored non-linear hybridization chain reaction (Panel-HCR) strategy is established for on-demand regulation of tumor-associated macrophages (TAMs). The Panel-HCR is composed of a recognition-then-assembly module and a release-then-regulation module. Upon recognizing tumor cells, a DNA nano-tree is assembled on the tumor cell surface and byproduct strands loaded with CpG oligodeoxynucleotides (CpG-ODNs) are released depending on the tumor cell concentration. The on-demand release of CpG-ODNs can achieve efficient regulation of M2 TAMs into the M1 phenotype. Throughout the recognition-then-assembly process, tumor cell-targeted bioimaging is implemented in single cells, fixed tissues, and living mice. Afterward, the on-demand release of CpG-ODNs regulate the transformation of M2 TAMs into the M1 phenotype by stimulating toll-like receptor 9 to activate the NF-κB pathway and increasing inflammatory cytokines. This release-then-regulation process is verified to induce strong antitumor immune responses both in vitro and in vivo. Altogether, this proposed strategy holds tremendous promise for on-demand antitumor immunotherapy.

DNA Aptamer Binding Octapeptide Repeat Region of Cellular Prion Protein.

Cellular prion protein (PrPC) is highly expressed in a variety of tumor cells and plays a crucial role in neurodegenerative diseases. Its N-terminal domain contains a conserved octapeptide (PHGGGWGQ) repeat sequence. The number of repeats has been correlated with the species as well as the development of associated diseases. Herein, PrPC was identified to be the molecular target of a high-affinity DNA aptamer HA5-68 obtained by cell-SELEX. Aptamer HA5-68 was further optimized to two short sequences (HA5-40-1 and HA5-40-2), and its binding site to PrPC was identified to be located in the loop-stem-loop region of the head of its secondary structure. HA5 series aptamers were demonstrated to bind the octapeptide repeat region of PrPC, as well as the synthesized peptides containing different numbers of octapeptide repeats. The PrPC expression on 42 cell lines was measured by using aptamer HA5-68 as a molecular probe. The clear understanding of the molecular structure and binding mechanism of this set of aptamers will provide information for the design of diagnostic methods and therapeutic drugs targeting PrPC.

The role of dietary fiber on preventing gestational diabetes mellitus in an at-risk group of high triglyceride-glucose index women: a randomized controlled trial.

BACKGROUND: Pregnant women with a high triglyceride-glucose (TyG) index during early pregnancy may increase the risk of gestational diabetes mellitus (GDM), and dietary fiber could play an important role in glucose and lipid metabolism. However, no trials have tested the effects of dietary fiber on preventing GDM in women with a high TyG index. This study aims to investigate whether GDM can be prevented by dietary fiber supplementation in women with a TyG index ≥8.5 during early pregnancy (<20 weeks). METHODS: A randomized clinical trial was performed among 295 women with a TyG index ≥8.5 before 20 weeks of gestation, divided into a fiber group (24 g dietary fiber powder/day) or a control group (usual care). The intervention was conducted from 20 to 24+6 gestational weeks, and both groups received guidance on exercise and diet. The primary outcomes were the incidence of GDM diagnosed by a 75 g oral glucose tolerance test at 25-28 gestational weeks, and levels of maternal blood glucose, lipids. Secondary outcomes include gestational hypertension, postpartum hemorrhage, preterm birth, and other maternal and neonatal complications. RESULTS: GDM occurred at 11.2% (10 of 89) in the fiber group, which was significantly lower than 23.7 (44 of 186) in the control group (P = 0.015). The mean gestational weeks increased dramatically in the fiber group compared with the control group (39.07 ± 1.08 vs. 38.58 ± 1.44 weeks, P = 0.006). The incidence of preterm birth was 2.3% (2 of 86) of women randomized to the fiber group compared with 9.4% (17 of 181) in the control group (P = 0.032). The concentrations of 2 h postprandial blood glucose showed statistically higher in the control group compared with the intervention group (6.69 ± 1.65 vs. 6.45 ± 1.25 mmol/L, P = 0.026). There were no other significant differences between groups in lipid profile values, or other secondary outcomes. CONCLUSION: An intervention with dietary fiber supplementation during pregnancy may prevent GDM and preterm birth in women with a TyG index ≥8.5 before 20 weeks of gestation.

CT and MR imaging features of soft tissue rhabdoid tumor: compared with rhabdomyosarcoma in children.

Objective: To assess the computed tomography (CT) and magnetic resonance (MR) imaging characteristics of soft tissue rhabdoid tumors (RT) and compare them with those of rhabdomyosarcoma (RMS). Methods: We conducted a retrospective analysis of 49 pediatric patients from 2011 to 2022, comprising 16 patients with soft tissue RT and 33 patients with RMS who underwent CT or MRI scans. Key imaging features, as well as clinical and pathological data, were compared between the two groups. The multivariate logistic regression analysis was used to determine independent differential factors for distinguishing soft tissue RT from RMS, and the model was established. The final prediction model was visualized by nomograms and verified internally by using a bootstrapped resample 1,000 times. The diagnostic accuracy of the combined model was assessed in terms of discrimination, calibration, and clinical utility. Results: Age, sex, number of lesions, and primary locations were similar in both groups. The imaging characteristics, including margin, calcification, surrounding blood vessels, and rim enhancement, were associated with the two groups of soft tissue tumors, as determined by univariate analysis (all p < 0.05). On multivariate logistic regression analysis, the presence of unclear margin (p-value, adjusted odds ratio [95% confidence interval]: 0.03, 7.96 [1.23, 51.67]) and calcification (0.012, 30.37 [2.09, 440.70]) were independent differential factors for predicting soft tissue RT over RMS. The presence of rim enhancement (0.007, 0.05 [0.01, 0.43]) was an independent differential factor for predicting RMS over soft tissue RT. The comprehensive model established by logistic regression analysis showed an AUC of 0.872 with 81.8% specificity and 81.3% sensitivity. The decision curve analysis (DCA) curve displayed that the model achieved a better net clinical benefit. Conclusion: Our study revealed that the image features of calcification, indistinct margins, and a lack of rim enhancement on CT and MRI might be reliable to distinguish soft tissue RT from RMS.

Structural Optimization and Interaction Study of a DNA Aptamer to L1 Cell Adhesion Molecule.

The L1 cell adhesion molecule (L1CAM) plays important roles in the development and plasticity of the nervous system as well as in tumor formation, progression, and metastasis. New ligands are necessary tools for biomedical research and the detection of L1CAM. Here, DNA aptamer yly12 against L1CAM was optimized to have much stronger binding affinity (10-24 fold) at room temperature and 37 °C via sequence mutation and extension. This interaction study revealed that the optimized aptamers (yly20 and yly21) adopted a hairpin structure containing two loops and two stems. The key nucleotides for aptamer binding mainly located in loop I and its adjacent area. Stem I mainly played the role of stabilizing the binding structure. The yly-series aptamers were demonstrated to bind the Ig6 domain of L1CAM. This study reveals a detailed molecular mechanism for the interaction between yly-series aptamers and L1CAM and provides guidance for drug development and detection probe design against L1CAM.

Modular Engineering of a DNA Tetrahedron-Based Nanomachine for Ultrasensitive Detection of Intracellular Bioactive Small Molecules.

Bioactive small molecules serve as invaluable biomarkers for recognizing modulated organismal metabolism in correlation with numerous diseases. Therefore, sensitive and specific molecular biosensing and imaging in vitro and in vivo are particularly critical for the diagnosis and treatment of a large group of diseases. Herein, a modular DNA tetrahedron-based nanomachine was engineered for the ultrasensitive detection of intracellular small molecules. The nanomachine was composed of three self-assembled modules: an aptamer for target recognition, an entropy-driven unit for signal reporting, and a tetrahedral oligonucleotide for the transportation of the cargo (e.g., the nanomachine and fluorescent markers). Adenosine triphosphate (ATP) was used as the molecular model. Once the target ATP bonded with the aptamer module, an initiator was released from the aptamer module to activate the entropy-driven module, ultimately activating the ATP-responsive signal output and subsequent signal amplification. The performance of the nanomachine was validated by delivering it to living cells with the aid of the tetrahedral module to demonstrate the possibility of executing intracellular ATP imaging. This innovative nanomachine displays a linear response to ATP in the 1 pM to 10 nM concentration range and demonstrates high sensitivity with a low detection limit of 0.40 pM. Remarkably, our nanomachine successfully executes endogenous ATP imaging and is able to distinguish tumor cells from normal ones based on the ATP level. Overall, the proposed strategy opens up a promising avenue for bioactive small molecule-based detection/diagnostic assays.

Identification and immuno-infiltration analysis of cuproptosis regulators in human spermatogenic dysfunction.

Introduction: Cuproptosis seems to promote the progression of diverse diseases. Hence, we explored the cuproptosis regulators in human spermatogenic dysfunction (SD), analyzed the condition of immune cell infiltration, and constructed a predictive model. Methods: Two microarray datasets (GSE4797 and GSE45885) related to male infertility (MI) patients with SD were downloaded from the Gene Expression Omnibus (GEO) database. We utilized the GSE4797 dataset to obtain differentially expressed cuproptosis-related genes (deCRGs) between SD and normal controls. The correlation between deCRGs and immune cell infiltration status was analyzed. We also explored the molecular clusters of CRGs and the status of immune cell infiltration. Notably, weighted gene co-expression network analysis (WGCNA) was used to identify the cluster-specific differentially expressed genes (DEGs). Moreso, gene set variation analysis (GSVA) was performed to annotate the enriched genes. Subsequently, we selected an optimal machine-learning model from four models. Finally, nomograms, calibration curves, decision curve analysis (DCA), and the GSE45885 dataset were utilized to verify the predictions' accuracy. Results: Among SD and normal controls, we confirmed that there are deCRGs and activated immune responses. Through the GSE4797 dataset, we obtained 11 deCRGs. ATP7A, ATP7B, SLC31A1, FDX1, PDHA1, PDHB, GLS, CDKN2A, DBT, and GCSH were highly expressed in testicular tissues with SD, whereas LIAS was lowly expressed. Additionally, two clusters were identified in SD. Immune-infiltration analysis showed the existing heterogeneity of immunity at these two clusters. Cuproptosis-related molecular Cluster2 was marked by enhanced expressions of ATP7A, SLC31A1, PDHA1, PDHB, CDKN2A, DBT, and higher proportions of resting memory CD4+ T cells. Furthermore, an eXtreme Gradient Boosting (XGB) model based on 5-gene was built, which showed superior performance on the external validation dataset GSE45885 (AUC = 0.812). Therefore, the combined nomogram, calibration curve, and DCA results demonstrated the accuracy of predicting SD. Conclusion: Our study preliminarily illustrates the relationship between SD and cuproptosis. Moreover, a bright predictive model was developed.

Sustainability assessment on paddy-upland crop rotations by carbon, nitrogen and water footprint integrated analysis: A field scale investigation.

Nutrients of carbon, nitrogen and water of farmland ecosystem are essential foundation to guarantee crop production, but also environmental flows associated greenhouse gas (GHG), reactive nitrogen (Nr) releases, and water consumption. Their flow characteristics serve as a crucial starting point for creating efficient management practices and mitigation measures. Therefore, the objectives of this study are to quantify the carbon footprint (CF), nitrogen footprint (NF), water footprint (WF), and comprehensive environmental footprint (ComF) of six paddy-upland rotation systems, including fallow-paddy rice (FA-PR), Chinese milk vetch-paddy rice (CMV-PR), wheat-paddy rice (WH-PR), rapeseed-paddy rice (RA-PR), green forage wheat-paddy rice (WF-PR), and vicia faba bean-paddy rice (FB-PR), as well as to analysis their relationships and define driving factors. Results showed that the lowest area-scaled CF of 3.74 t CO2-eq ha-1 were observed in the CMV-PR rotation, which were 41% lower than that for WH-PR (the highest CF, 9.13 t CO2-eq ha-1) when soil carbon change was taken into account. It is of importance that soil carbon sequestration in CMV-PR rotation could offset up to around 57% of its CF, while the WH-PR rotation only offset 25%. The RA-PR rotation had the highest area-scaled NF and WF, which was 1.8 and 1.9 times greater than those of the lowest rotation in FA-PR. In terms of comprehensive environmental effects, the six rotation systems showed the order of FA-PR < CMV-PR < FB-PR < RA-PR < WF-PR < WH-PR, with NH3 volatilization accounting 60.7%-66.7% and blue-green WF for 17.5%-26.6% of the total. Therefore, priority should be given to optimizing N fertilizer application and water consumption for paddy-upland rotation systems. The study also suggested that appropriate inter-annual adjustment of rotation system could contribute to achieving GHG mitigations and Nr losses.